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  1. S Yamashita, E Kimura, N Tawara, H Sakaguchi, T Nakama, Y Maeda, T Hirano, M Uchino and Y Ando.
    Optineurin is potentially associated with TDP-43 and involved in the pathogenesis of inclusion body myositis.. Neuropathology and applied neurobiology 39(4):406–16, June 2013.
    Abstract AIMS: Increasing evidences suggest a similarity in the pathophysiological mechanisms of neuronal cell death in amyotrophic lateral sclerosis (ALS) and myofibre degeneration in sporadic inclusion body myositis (sIBM). The aim of this study is to elucidate the involvement of ALS-causing proteins in the pathophysiological mechanisms in sIBM. METHODS: Skeletal muscle biopsy specimens of five patients with sIBM, two with oculopharyngeal muscular dystrophy (OPMD), three with polymyositis (PM), three with dermatomyositis (DM), three with neurogenic muscular atrophy, and three healthy control subjects were examined. We analysed the expression and localization of familial ALS-causing proteins, including transactive response DNA binding protein-43 (TDP-43), fused in sarcoma/translocated in liposarcoma (FUS/TLS), Cu/Zn superoxide dismutase (SOD1) and optineurin (OPTN) by immunohistochemistry. RESULTS: TDP-43, OPTN and, to a lesser extent, FUS/TLS were more frequently accumulated in the cytoplasm in patients with sIBM and OPMD than in patients with PM, DM, neurogenic muscular atrophy, or healthy control subjects. SOD1 was accumulated in a small percentage of myofibres in patients with sIBM and OPMD, and to a very small extent in patients with PM and DM. Confocal microscopy imaging showed that TDP-43 proteins more often colocalized with OPTN than with FUS/TLS, p62 and phosphorylated Tau. CONCLUSIONS: These findings suggest that OPTN in cooperation with TDP-43 might be involved in the pathophysiological mechanisms of skeletal muscular degeneration in myopathy with rimmed vacuoles. Further investigation into these mechanisms is therefore warranted.
    URL, DOI BibTeX

    @article{Yamashita2013,
    	abstract = "AIMS: Increasing evidences suggest a similarity in the pathophysiological mechanisms of neuronal cell death in amyotrophic lateral sclerosis (ALS) and myofibre degeneration in sporadic inclusion body myositis (sIBM). The aim of this study is to elucidate the involvement of ALS-causing proteins in the pathophysiological mechanisms in sIBM. METHODS: Skeletal muscle biopsy specimens of five patients with sIBM, two with oculopharyngeal muscular dystrophy (OPMD), three with polymyositis (PM), three with dermatomyositis (DM), three with neurogenic muscular atrophy, and three healthy control subjects were examined. We analysed the expression and localization of familial ALS-causing proteins, including transactive response DNA binding protein-43 (TDP-43), fused in sarcoma/translocated in liposarcoma (FUS/TLS), Cu/Zn superoxide dismutase (SOD1) and optineurin (OPTN) by immunohistochemistry. RESULTS: TDP-43, OPTN and, to a lesser extent, FUS/TLS were more frequently accumulated in the cytoplasm in patients with sIBM and OPMD than in patients with PM, DM, neurogenic muscular atrophy, or healthy control subjects. SOD1 was accumulated in a small percentage of myofibres in patients with sIBM and OPMD, and to a very small extent in patients with PM and DM. Confocal microscopy imaging showed that TDP-43 proteins more often colocalized with OPTN than with FUS/TLS, p62 and phosphorylated Tau. CONCLUSIONS: These findings suggest that OPTN in cooperation with TDP-43 might be involved in the pathophysiological mechanisms of skeletal muscular degeneration in myopathy with rimmed vacuoles. Further investigation into these mechanisms is therefore warranted.",
    	author = "Yamashita, S and Kimura, E and Tawara, N and Sakaguchi, H and Nakama, T and Maeda, Y and Hirano, T and Uchino, M and Ando, Y",
    	doi = "10.1111/j.1365-2990.2012.01297.x",
    	issn = "1365-2990",
    	journal = "Neuropathology and applied neurobiology",
    	keywords = "Adult,Aged,Aged, 80 and over,Amyotrophic Lateral Sclerosis,Amyotrophic Lateral Sclerosis: genetics,Amyotrophic Lateral Sclerosis: pathology,Biopsy,DNA-Binding Proteins,DNA-Binding Proteins: genetics,DNA-Binding Proteins: physiology,Dermatomyositis,Dermatomyositis: genetics,Dermatomyositis: pathology,Female,Humans,Immunohistochemistry,Male,Middle Aged,Muscular Atrophy,Muscular Atrophy: genetics,Muscular Atrophy: pathology,Muscular Dystrophy, Oculopharyngeal,Muscular Dystrophy, Oculopharyngeal: genetics,Muscular Dystrophy, Oculopharyngeal: pathology,Myositis, Inclusion Body,Myositis, Inclusion Body: genetics,Myositis, Inclusion Body: pathology,Polymyositis,Polymyositis: genetics,Polymyositis: pathology,RNA-Binding Protein FUS,RNA-Binding Protein FUS: metabolism,Superoxide Dismutase,Superoxide Dismutase: metabolism,TDP-43 Proteinopathies,TDP-43 Proteinopathies: genetics,TDP-43 Proteinopathies: pathology,Transcription Factor TFIIIA,Transcription Factor TFIIIA: genetics,Transcription Factor TFIIIA: physiology",
    	month = "jun",
    	number = 4,
    	pages = "406--16",
    	pmid = 22860700,
    	title = "{Optineurin is potentially associated with TDP-43 and involved in the pathogenesis of inclusion body myositis.}",
    	url = "http://www.ncbi.nlm.nih.gov/pubmed/22860700",
    	volume = 39,
    	year = 2013
    }
    
  2. Hirofumi Maruyama and Hideshi Kawakami.
    Optineurin and amyotrophic lateral sclerosis.. Geriatrics & gerontology international 13(3):528–32, 2013.
    Abstract Amyotrophic lateral sclerosis is a devastating disease, and thus it is important to identify the causative gene and resolve the mechanism of the disease. We identified optineurin as a causative gene for amyotrophic lateral sclerosis. We found three types of mutations: a homozygous deletion of exon 5, a homozygous Q398X nonsense mutation and a heterozygous E478G missense mutation within its ubiquitin-binding domain. Optineurin negatively regulates the tumor necrosis factor-$\alpha$-induced activation of nuclear factor kappa B. Nonsense and missense mutations abolished this function. Mutations related to amyotrophic lateral sclerosis also negated the inhibition of interferon regulatory factor-3. The missense mutation showed a cyotoplasmic distribution different from that of the wild type. There are no specific clinical symptoms related to optineurin. However, severe brain atrophy was detected in patients with homozygous deletion. Neuropathologically, an E478G patient showed transactive response DNA-binding protein of 43 kDa-positive neuronal intracytoplasmic inclusions in the spinal and medullary motor neurons. Furthermore, Golgi fragmentation was identified in 73% of this patient's anterior horn cells. In addition, optineurin is colocalized with fused in sarcoma in the basophilic inclusions of amyotrophic lateral sclerosis with fused in sarcoma mutations, and in basophilic inclusion body disease. These findings strongly suggest that optineurin is involved in the pathogenesis of amyotrophic lateral sclerosis.
    URL, DOI BibTeX

    @article{Maruyama2013,
    	abstract = "Amyotrophic lateral sclerosis is a devastating disease, and thus it is important to identify the causative gene and resolve the mechanism of the disease. We identified optineurin as a causative gene for amyotrophic lateral sclerosis. We found three types of mutations: a homozygous deletion of exon 5, a homozygous Q398X nonsense mutation and a heterozygous E478G missense mutation within its ubiquitin-binding domain. Optineurin negatively regulates the tumor necrosis factor-$\alpha$-induced activation of nuclear factor kappa B. Nonsense and missense mutations abolished this function. Mutations related to amyotrophic lateral sclerosis also negated the inhibition of interferon regulatory factor-3. The missense mutation showed a cyotoplasmic distribution different from that of the wild type. There are no specific clinical symptoms related to optineurin. However, severe brain atrophy was detected in patients with homozygous deletion. Neuropathologically, an E478G patient showed transactive response DNA-binding protein of 43 kDa-positive neuronal intracytoplasmic inclusions in the spinal and medullary motor neurons. Furthermore, Golgi fragmentation was identified in 73\% of this patient's anterior horn cells. In addition, optineurin is colocalized with fused in sarcoma in the basophilic inclusions of amyotrophic lateral sclerosis with fused in sarcoma mutations, and in basophilic inclusion body disease. These findings strongly suggest that optineurin is involved in the pathogenesis of amyotrophic lateral sclerosis.",
    	author = "Maruyama, Hirofumi and Kawakami, Hideshi",
    	doi = "10.1111/ggi.12022",
    	issn = "1447-0594",
    	journal = "Geriatrics \& gerontology international",
    	keywords = "Amyotrophic Lateral Sclerosis,Amyotrophic Lateral Sclerosis: epidemiology,Amyotrophic Lateral Sclerosis: genetics,Amyotrophic Lateral Sclerosis: metabolism,DNA,DNA: genetics,Disease Progression,Genetic Predisposition to Disease,Humans,Mutation,Prevalence,Transcription Factor TFIIIA,Transcription Factor TFIIIA: genetics,Transcription Factor TFIIIA: metabolism,World Health",
    	month = "",
    	number = 3,
    	pages = "528--32",
    	pmid = 23279185,
    	title = "{Optineurin and amyotrophic lateral sclerosis.}",
    	url = "http://www.ncbi.nlm.nih.gov/pubmed/23279185",
    	volume = 13,
    	year = 2013
    }
    
  3. Jelena Korac, Veronique Schaeffer, Igor Kovacevic, Albrecht M Clement, Benno Jungblut, Christian Behl, Janos Terzic and Ivan Dikic.
    Ubiquitin-independent function of optineurin in autophagic clearance of protein aggregates.. Journal of cell science 126(Pt 2):580–92, 2013.
    Abstract Aggregation of misfolded proteins and the associated loss of neurons are considered a hallmark of numerous neurodegenerative diseases. Optineurin is present in protein inclusions observed in various neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), Huntington's disease, Alzheimer's disease, Parkinson's disease, Creutzfeld-Jacob disease and Pick's disease. Optineurin deletion mutations have also been described in ALS patients. However, the role of optineurin in mechanisms of protein aggregation remains unclear. In this report, we demonstrate that optineurin recognizes various protein aggregates via its C-terminal coiled-coil domain in a ubiquitin-independent manner. We also show that optineurin depletion significantly increases protein aggregation in HeLa cells and that morpholino-silencing of the optineurin ortholog in zebrafish causes the motor axonopathy phenotype similar to a zebrafish model of ALS. A more severe phenotype is observed when optineurin is depleted in zebrafish carrying ALS mutations. Furthermore, TANK1 binding kinase 1 (TBK1) is colocalized with optineurin on protein aggregates and is important in clearance of protein aggregates through the autophagy-lysosome pathway. TBK1 phosphorylates optineurin at serine 177 and regulates its ability to interact with autophagy modifiers. This study provides evidence for a ubiquitin-independent function of optineurin in autophagic clearance of protein aggregates as well as additional relevance for TBK1 as an upstream regulator of the autophagic pathway.
    URL, DOI BibTeX

    @article{Korac2013,
    	abstract = "Aggregation of misfolded proteins and the associated loss of neurons are considered a hallmark of numerous neurodegenerative diseases. Optineurin is present in protein inclusions observed in various neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), Huntington's disease, Alzheimer's disease, Parkinson's disease, Creutzfeld-Jacob disease and Pick's disease. Optineurin deletion mutations have also been described in ALS patients. However, the role of optineurin in mechanisms of protein aggregation remains unclear. In this report, we demonstrate that optineurin recognizes various protein aggregates via its C-terminal coiled-coil domain in a ubiquitin-independent manner. We also show that optineurin depletion significantly increases protein aggregation in HeLa cells and that morpholino-silencing of the optineurin ortholog in zebrafish causes the motor axonopathy phenotype similar to a zebrafish model of ALS. A more severe phenotype is observed when optineurin is depleted in zebrafish carrying ALS mutations. Furthermore, TANK1 binding kinase 1 (TBK1) is colocalized with optineurin on protein aggregates and is important in clearance of protein aggregates through the autophagy-lysosome pathway. TBK1 phosphorylates optineurin at serine 177 and regulates its ability to interact with autophagy modifiers. This study provides evidence for a ubiquitin-independent function of optineurin in autophagic clearance of protein aggregates as well as additional relevance for TBK1 as an upstream regulator of the autophagic pathway.",
    	author = "Korac, Jelena and Schaeffer, Veronique and Kovacevic, Igor and Clement, Albrecht M and Jungblut, Benno and Behl, Christian and Terzic, Janos and Dikic, Ivan",
    	doi = "10.1242/jcs.114926",
    	issn = "1477-9137",
    	journal = "Journal of cell science",
    	keywords = "Animals,Autophagy,Autophagy: physiology,Disease Models, Animal,HeLa Cells,Humans,Mice,Mice, Inbred C57BL,Mice, Transgenic,Neurodegenerative Diseases,Neurodegenerative Diseases: genetics,Neurodegenerative Diseases: metabolism,Phosphorylation,Protein Binding,Transcription Factor TFIIIA,Transcription Factor TFIIIA: metabolism,Ubiquitin,Ubiquitin: metabolism,Zebrafish",
    	month = "",
    	number = "Pt 2",
    	pages = "580--92",
    	pmid = 23178947,
    	title = "{Ubiquitin-independent function of optineurin in autophagic clearance of protein aggregates.}",
    	url = "http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3654196\&tool=pmcentrez\&rendertype=abstract",
    	volume = 126,
    	year = 2013
    }
    
  4. Anna M Blokhuis, Ewout J N Groen, Max Koppers, Leonard H Berg and Jeroen R Pasterkamp.
    Protein aggregation in amyotrophic lateral sclerosis.. Acta neuropathologica 125(6):777–94, 2013.
    Abstract Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the aggregation of ubiquitinated proteins in affected motor neurons. Recent studies have identified several new molecular constituents of ALS-linked cellular aggregates, including FUS, TDP-43, OPTN, UBQLN2 and the translational product of intronic repeats in the gene C9ORF72. Mutations in the genes encoding these proteins are found in a subgroup of ALS patients and segregate with disease in familial cases, indicating a causal relationship with disease pathogenesis. Furthermore, these proteins are often detected in aggregates of non-mutation carriers and those observed in other neurodegenerative disorders, supporting a widespread role in neuronal degeneration. The molecular characteristics and distribution of different types of protein aggregates in ALS can be linked to specific genetic alterations and shows a remarkable overlap hinting at a convergence of underlying cellular processes and pathological effects. Thus far, self-aggregating properties of prion-like domains, altered RNA granule formation and dysfunction of the protein quality control system have been suggested to contribute to protein aggregation in ALS. The precise pathological effects of protein aggregation remain largely unknown, but experimental evidence hints at both gain- and loss-of-function mechanisms. Here, we discuss recent advances in our understanding of the molecular make-up, formation, and mechanism-of-action of protein aggregates in ALS. Further insight into protein aggregation will not only deepen our understanding of ALS pathogenesis but also may provide novel avenues for therapeutic intervention.
    URL, DOI BibTeX

    @article{Blokhuis2013,
    	abstract = "Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the aggregation of ubiquitinated proteins in affected motor neurons. Recent studies have identified several new molecular constituents of ALS-linked cellular aggregates, including FUS, TDP-43, OPTN, UBQLN2 and the translational product of intronic repeats in the gene C9ORF72. Mutations in the genes encoding these proteins are found in a subgroup of ALS patients and segregate with disease in familial cases, indicating a causal relationship with disease pathogenesis. Furthermore, these proteins are often detected in aggregates of non-mutation carriers and those observed in other neurodegenerative disorders, supporting a widespread role in neuronal degeneration. The molecular characteristics and distribution of different types of protein aggregates in ALS can be linked to specific genetic alterations and shows a remarkable overlap hinting at a convergence of underlying cellular processes and pathological effects. Thus far, self-aggregating properties of prion-like domains, altered RNA granule formation and dysfunction of the protein quality control system have been suggested to contribute to protein aggregation in ALS. The precise pathological effects of protein aggregation remain largely unknown, but experimental evidence hints at both gain- and loss-of-function mechanisms. Here, we discuss recent advances in our understanding of the molecular make-up, formation, and mechanism-of-action of protein aggregates in ALS. Further insight into protein aggregation will not only deepen our understanding of ALS pathogenesis but also may provide novel avenues for therapeutic intervention.",
    	author = "Blokhuis, Anna M and Groen, Ewout J N and Koppers, Max and van den Berg, Leonard H and Pasterkamp, R Jeroen",
    	doi = "10.1007/s00401-013-1125-6",
    	issn = "1432-0533",
    	journal = "Acta neuropathologica",
    	keywords = "Amyotrophic Lateral Sclerosis,Amyotrophic Lateral Sclerosis: etiology,Amyotrophic Lateral Sclerosis: metabolism,Amyotrophic Lateral Sclerosis: pathology,Cell Cycle Proteins,Cell Cycle Proteins: physiology,DNA-Binding Proteins,DNA-Binding Proteins: physiology,Humans,Inclusion Bodies,Inclusion Bodies: physiology,Nerve Tissue Proteins,Nerve Tissue Proteins: physiology,Proteins,Proteins: physiology,Proteolysis,RNA-Binding Protein FUS,RNA-Binding Protein FUS: physiology,Transcription Factor TFIIIA,Transcription Factor TFIIIA: physiology,Ubiquitins,Ubiquitins: physiology",
    	month = "",
    	number = 6,
    	pages = "777--94",
    	pmid = 23673820,
    	title = "{Protein aggregation in amyotrophic lateral sclerosis.}",
    	url = "http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3661910\&tool=pmcentrez\&rendertype=abstract",
    	volume = 125,
    	year = 2013
    }
    
  5. David Kachaner, Pierre Génin, Emmanuel Laplantine and Robert Weil.
    Toward an integrative view of Optineurin functions.. Cell cycle (Georgetown, Tex.) 11(15):2808–18, August 2012.
    Abstract This review highlights recent advances in our understanding of the mechanisms of Optineurin (Optn) action and its implication in diseases. Optn has emerged as a key player regulating various physiological processes, including membrane trafficking, protein secretion, cell division and host defense against pathogens. Furthermore, there is growing evidence for an association of Optn mutations with human diseases such as primary open-angle glaucoma, amyotrophic lateral sclerosis and Paget's disease of bone. Optn functions depend on its precise subcellular localization and its interaction with other proteins. Here, we review the mechanisms that allow Optn to ensure a timely and spatially coordinated integration of different physiological processes and discuss how their deregulation may lead to different pathologies.
    URL, DOI BibTeX

    @article{Kachaner2012,
    	abstract = "This review highlights recent advances in our understanding of the mechanisms of Optineurin (Optn) action and its implication in diseases. Optn has emerged as a key player regulating various physiological processes, including membrane trafficking, protein secretion, cell division and host defense against pathogens. Furthermore, there is growing evidence for an association of Optn mutations with human diseases such as primary open-angle glaucoma, amyotrophic lateral sclerosis and Paget's disease of bone. Optn functions depend on its precise subcellular localization and its interaction with other proteins. Here, we review the mechanisms that allow Optn to ensure a timely and spatially coordinated integration of different physiological processes and discuss how their deregulation may lead to different pathologies.",
    	author = "Kachaner, David and G\'{e}nin, Pierre and Laplantine, Emmanuel and Weil, Robert",
    	doi = "10.4161/cc.20946",
    	issn = "1551-4005",
    	journal = "Cell cycle (Georgetown, Tex.)",
    	keywords = "Amyotrophic Lateral Sclerosis,Amyotrophic Lateral Sclerosis: genetics,Animals,Apoptosis,Biological Transport,Cell Division,Glaucoma,Glaucoma: genetics,Humans,NF-kappa B,NF-kappa B: metabolism,Osteitis Deformans,Osteitis Deformans: genetics,Transcription Factor TFIIIA,Transcription Factor TFIIIA: genetics,Transcription Factor TFIIIA: physiology",
    	month = "aug",
    	number = 15,
    	pages = "2808--18",
    	pmid = 22801549,
    	title = "{Toward an integrative view of Optineurin functions.}",
    	url = "http://www.ncbi.nlm.nih.gov/pubmed/22801549",
    	volume = 11,
    	year = 2012
    }
    
  6. Hongyu Ying and Beatrice Y J T Yue.
    Cellular and molecular biology of optineurin.. International review of cell and molecular biology 294:223–58, January 2012.
    Abstract Optineurin is a gene linked to glaucoma, amyotrophic lateral sclerosis, other neurodegenerative diseases, and Paget's disease of bone. This review describes the characteristics of optineurin and summarizes the cellular and molecular biology investigations conducted so far on optineurin. Data from a number of laboratories indicate that optineurin is a cytosolic protein containing 577 amino acid residues. Interacting with proteins such as myosin VI, Rab8, huntingtin, transferrin receptor, and TANK-binding kinase 1, optineurin is involved in basic cellular functions including protein trafficking, maintenance of the Golgi apparatus, as well as NF-$\kappa$B pathway, antiviral, and antibacteria signaling. Mutation or alteration of homeostasis of optineurin (such as overexpression or knockdown) results in adverse consequences in the cells, leading to the development of neurodegenerative diseases including glaucoma.
    URL, DOI BibTeX

    @article{Ying2012,
    	abstract = "Optineurin is a gene linked to glaucoma, amyotrophic lateral sclerosis, other neurodegenerative diseases, and Paget's disease of bone. This review describes the characteristics of optineurin and summarizes the cellular and molecular biology investigations conducted so far on optineurin. Data from a number of laboratories indicate that optineurin is a cytosolic protein containing 577 amino acid residues. Interacting with proteins such as myosin VI, Rab8, huntingtin, transferrin receptor, and TANK-binding kinase 1, optineurin is involved in basic cellular functions including protein trafficking, maintenance of the Golgi apparatus, as well as NF-$\kappa$B pathway, antiviral, and antibacteria signaling. Mutation or alteration of homeostasis of optineurin (such as overexpression or knockdown) results in adverse consequences in the cells, leading to the development of neurodegenerative diseases including glaucoma.",
    	author = "Ying, Hongyu and Yue, Beatrice Y J T",
    	doi = "10.1016/B978-0-12-394305-7.00005-7",
    	issn = "1937-6448",
    	journal = "International review of cell and molecular biology",
    	keywords = "Animals,Anti-Bacterial Agents,Anti-Bacterial Agents: chemistry,Anti-Bacterial Agents: metabolism,Antiviral Agents,Antiviral Agents: chemistry,Antiviral Agents: metabolism,Golgi Apparatus,Golgi Apparatus: chemistry,Golgi Apparatus: metabolism,Humans,Protein Transport,Protein Transport: physiology,Signal Transduction,Signal Transduction: genetics,Signal Transduction: physiology,Transcription Factor TFIIIA,Transcription Factor TFIIIA: chemistry,Transcription Factor TFIIIA: genetics,Transcription Factor TFIIIA: physiology",
    	month = "jan",
    	pages = "223--58",
    	pmid = 22364875,
    	title = "{Cellular and molecular biology of optineurin.}",
    	url = "http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3673586\&tool=pmcentrez\&rendertype=abstract",
    	volume = 294,
    	year = 2012
    }
    
  7. Claudia Schwab, Sheng Yu, Edith G McGeer and Patrick L McGeer.
    Optineurin in Huntington's disease intranuclear inclusions.. Neuroscience letters 506(1):149–54, January 2012.
    Abstract Optineurin mutations cause adult-onset primary open-angle glaucoma and have been associated with some familial forms of amyotrophic lateral sclerosis (ALS). Optineurin is involved in many cellular processes and interacts with a variety of proteins, among them huntingtin (htt). Here we report that in Huntington's disease (HD) cortex, optineurin frequently occurs in neuronal intranuclear inclusions, and to a lesser extent, in inclusions in the neuropil and in perikarya. Most intranuclear optineurin-positive inclusions were co-labeled for ubiquitin, but they were only occasionally and more weakly co-labeled for htt. Optineurin-labeled neuropil and perikaryal inclusions were commonly co-labeled for ubiquitin and htt. Although these inclusions were common in cortex, they were rare in striatum. Our results show that in HD optineurin is present in intranuclear, neuropil and perikaryal inclusions. It is not clear whether this indicates a primary involvement in the disease process. In HD, the known interaction of htt and optineurin may suggest that a different process takes place as compared to other neurodegenerative disorders.
    URL, DOI BibTeX

    @article{Schwab2012,
    	abstract = "Optineurin mutations cause adult-onset primary open-angle glaucoma and have been associated with some familial forms of amyotrophic lateral sclerosis (ALS). Optineurin is involved in many cellular processes and interacts with a variety of proteins, among them huntingtin (htt). Here we report that in Huntington's disease (HD) cortex, optineurin frequently occurs in neuronal intranuclear inclusions, and to a lesser extent, in inclusions in the neuropil and in perikarya. Most intranuclear optineurin-positive inclusions were co-labeled for ubiquitin, but they were only occasionally and more weakly co-labeled for htt. Optineurin-labeled neuropil and perikaryal inclusions were commonly co-labeled for ubiquitin and htt. Although these inclusions were common in cortex, they were rare in striatum. Our results show that in HD optineurin is present in intranuclear, neuropil and perikaryal inclusions. It is not clear whether this indicates a primary involvement in the disease process. In HD, the known interaction of htt and optineurin may suggest that a different process takes place as compared to other neurodegenerative disorders.",
    	author = "Schwab, Claudia and Yu, Sheng and McGeer, Edith G and McGeer, Patrick L",
    	doi = "10.1016/j.neulet.2011.10.070",
    	issn = "1872-7972",
    	journal = "Neuroscience letters",
    	keywords = "Adult,Aged,Aged, 80 and over,Brain,Brain: pathology,Brain: ultrastructure,Female,Humans,Huntington Disease,Huntington Disease: pathology,Intranuclear Inclusion Bodies,Intranuclear Inclusion Bodies: metabolism,Male,Middle Aged,Nerve Tissue Proteins,Nerve Tissue Proteins: metabolism,Neurofilament Proteins,Neurofilament Proteins: metabolism,Nuclear Proteins,Nuclear Proteins: metabolism,Transcription Factor TFIIIA,Transcription Factor TFIIIA: metabolism,Ubiquitin,Ubiquitin: metabolism",
    	month = "jan",
    	number = 1,
    	pages = "149--54",
    	pmid = 22085693,
    	title = "{Optineurin in Huntington's disease intranuclear inclusions.}",
    	url = "http://www.ncbi.nlm.nih.gov/pubmed/22085693",
    	volume = 506,
    	year = 2012
    }
    
  8. Hidefumi Ito, Kengo Fujita, Masataka Nakamura, Reika Wate, Satoshi Kaneko, Shoichi Sasaki, Kiyomi Yamane, Naoki Suzuki, Masashi Aoki, Noriyuki Shibata, Shinji Togashi, Akihiro Kawata, Yoko Mochizuki, Toshio Mizutani, Hirofumi Maruyama, Asao Hirano, Ryosuke Takahashi, Hideshi Kawakami and Hirofumi Kusaka.
    Optineurin is co-localized with FUS in basophilic inclusions of ALS with FUS mutation and in basophilic inclusion body disease.. Acta neuropathologica 121(4):555–7, April 2011.
    URL, DOI BibTeX

    @article{Ito2011,
    	author = "Ito, Hidefumi and Fujita, Kengo and Nakamura, Masataka and Wate, Reika and Kaneko, Satoshi and Sasaki, Shoichi and Yamane, Kiyomi and Suzuki, Naoki and Aoki, Masashi and Shibata, Noriyuki and Togashi, Shinji and Kawata, Akihiro and Mochizuki, Yoko and Mizutani, Toshio and Maruyama, Hirofumi and Hirano, Asao and Takahashi, Ryosuke and Kawakami, Hideshi and Kusaka, Hirofumi",
    	doi = "10.1007/s00401-011-0809-z",
    	issn = "1432-0533",
    	journal = "Acta neuropathologica",
    	keywords = "Adult,Amyotrophic Lateral Sclerosis,Amyotrophic Lateral Sclerosis: genetics,Amyotrophic Lateral Sclerosis: metabolism,Amyotrophic Lateral Sclerosis: pathology,Basophils,Basophils: pathology,DNA-Binding Proteins,DNA-Binding Proteins: metabolism,Female,Humans,Inclusion Bodies,Inclusion Bodies: metabolism,Inclusion Bodies: pathology,Male,Middle Aged,RNA-Binding Protein FUS,RNA-Binding Protein FUS: genetics,RNA-Binding Protein FUS: metabolism,Superoxide Dismutase,Superoxide Dismutase: metabolism,Transcription Factor TFIIIA,Transcription Factor TFIIIA: metabolism",
    	month = "apr",
    	number = 4,
    	pages = "555--7",
    	pmid = 21327942,
    	title = "{Optineurin is co-localized with FUS in basophilic inclusions of ALS with FUS mutation and in basophilic inclusion body disease.}",
    	url = "http://www.ncbi.nlm.nih.gov/pubmed/21327942",
    	volume = 121,
    	year = 2011
    }
    
  9. Takemasa Sakaguchi, Takashi Irie, Ryoko Kawabata, Asuka Yoshida, Hirofumi Maruyama and Hideshi Kawakami.
    Optineurin with amyotrophic lateral sclerosis-related mutations abrogates inhibition of interferon regulatory factor-3 activation.. Neuroscience letters 505(3):279–81, 2011.
    Abstract Optineurin has been shown to be involved in primary open-angle glaucoma. We recently found that optineurin is involved in familial amyotrophic lateral sclerosis (ALS). On the other hand, optineurin has been shown to inhibit transcription factors related to innate immunity such as NF-$\kappa$B and interferon regulatory factor-3 (IRF3). In the present study, the effect of ALS-associated optineurin mutations on IRF3 activation was investigated. Optineurin inhibited IRF3 activation induced by melanoma differentiation-associated gene 5 or Toll-IL-1 receptor domain-containing adaptor-inducing interferon-$\beta$. The inhibition was abrogated by mutations related to ALS but not by a mutation related to glaucoma. Reporter assay indicated that the JAK-STAT signaling pathway was not affected by optineurin. These results show that ALS-related optineurin is involved in the IRF3 activation pathway. Pathogenesis of ALS may be associated with some kind of innate immunity, especially that against virus infection, through IRF3 activation.
    URL, DOI BibTeX

    @article{Sakaguchi2011,
    	abstract = "Optineurin has been shown to be involved in primary open-angle glaucoma. We recently found that optineurin is involved in familial amyotrophic lateral sclerosis (ALS). On the other hand, optineurin has been shown to inhibit transcription factors related to innate immunity such as NF-$\kappa$B and interferon regulatory factor-3 (IRF3). In the present study, the effect of ALS-associated optineurin mutations on IRF3 activation was investigated. Optineurin inhibited IRF3 activation induced by melanoma differentiation-associated gene 5 or Toll-IL-1 receptor domain-containing adaptor-inducing interferon-$\beta$. The inhibition was abrogated by mutations related to ALS but not by a mutation related to glaucoma. Reporter assay indicated that the JAK-STAT signaling pathway was not affected by optineurin. These results show that ALS-related optineurin is involved in the IRF3 activation pathway. Pathogenesis of ALS may be associated with some kind of innate immunity, especially that against virus infection, through IRF3 activation.",
    	author = "Sakaguchi, Takemasa and Irie, Takashi and Kawabata, Ryoko and Yoshida, Asuka and Maruyama, Hirofumi and Kawakami, Hideshi",
    	doi = "10.1016/j.neulet.2011.10.040",
    	issn = "1872-7972",
    	journal = "Neuroscience letters",
    	keywords = "Cell Line, Transformed,DEAD-box RNA Helicases,DEAD-box RNA Helicases: genetics,DEAD-box RNA Helicases: metabolism,Epithelial Cells,Epithelial Cells: metabolism,Epithelial Cells: physiology,Gene Expression Regulation,Gene Expression Regulation: genetics,Green Fluorescent Proteins,Green Fluorescent Proteins: genetics,Humans,Interferon Regulatory Factor-3,Interferon Regulatory Factor-3: genetics,Interferon Regulatory Factor-3: metabolism,Models, Biological,Mutation,Mutation: genetics,Transcription Factor TFIIIA,Transcription Factor TFIIIA: genetics,Transfection,Transfection: methods",
    	month = "",
    	number = 3,
    	pages = "279--81",
    	pmid = 22040667,
    	title = "{Optineurin with amyotrophic lateral sclerosis-related mutations abrogates inhibition of interferon regulatory factor-3 activation.}",
    	url = "http://www.ncbi.nlm.nih.gov/pubmed/22040667",
    	volume = 505,
    	year = 2011
    }
    
  10. Tenshi Osawa, Yuji Mizuno, Yukio Fujita, Masamitsu Takatama, Yoichi Nakazato and Koichi Okamoto.
    Optineurin in neurodegenerative diseases.. Neuropathology : official journal of the Japanese Society of Neuropathology 31(6):569–74, 2011.
    Abstract Optineurin is a gene associated with normal tension glaucoma and primary open-angle glaucoma, one of the major causes of irreversible bilateral blindness. Recently, mutations in the gene encoding optineurin were found in patients with amyotrophic lateral sclerosis (ALS). Immunohistochemical analysis showed aggregation of optineurin in skein-like inclusions and round hyaline inclusions in the spinal cord, suggesting that optineurin appears to be a more general marker for ALS. However, our detailed examinations demonstrated that optineurin was found not only in ALS-associated pathological structures, but also in ubiquitin-positive intraneuronal inclusions in ALS with dementia, basophilic inclusions in the basophilic type of ALS, neurofibrillary tangles and dystrophic neurites in Alzheimer's disease, Lewy bodies and Lewy neurites in Parkinson's disease, ballooned neurons in Creutzfeldt-Jakob disease, glial cytoplasmic inclusions in multiple system atrophy, and Pick bodies in Pick disease. With respect to optineurin-positive basophilic inclusions, these structures showed variable immunoreactivities for ubiquitin; some structures were obviously ubiquitin-positive, while others were negative for the protein, suggesting that optineurin expression was not always associated with the expression of ubiquitin. This study indicates that optineurin is widely distributed in neurodegenerative conditions; however, its significance is obscure.
    URL, DOI BibTeX

    @article{Osawa2011,
    	abstract = "Optineurin is a gene associated with normal tension glaucoma and primary open-angle glaucoma, one of the major causes of irreversible bilateral blindness. Recently, mutations in the gene encoding optineurin were found in patients with amyotrophic lateral sclerosis (ALS). Immunohistochemical analysis showed aggregation of optineurin in skein-like inclusions and round hyaline inclusions in the spinal cord, suggesting that optineurin appears to be a more general marker for ALS. However, our detailed examinations demonstrated that optineurin was found not only in ALS-associated pathological structures, but also in ubiquitin-positive intraneuronal inclusions in ALS with dementia, basophilic inclusions in the basophilic type of ALS, neurofibrillary tangles and dystrophic neurites in Alzheimer's disease, Lewy bodies and Lewy neurites in Parkinson's disease, ballooned neurons in Creutzfeldt-Jakob disease, glial cytoplasmic inclusions in multiple system atrophy, and Pick bodies in Pick disease. With respect to optineurin-positive basophilic inclusions, these structures showed variable immunoreactivities for ubiquitin; some structures were obviously ubiquitin-positive, while others were negative for the protein, suggesting that optineurin expression was not always associated with the expression of ubiquitin. This study indicates that optineurin is widely distributed in neurodegenerative conditions; however, its significance is obscure.",
    	author = "Osawa, Tenshi and Mizuno, Yuji and Fujita, Yukio and Takatama, Masamitsu and Nakazato, Yoichi and Okamoto, Koichi",
    	doi = "10.1111/j.1440-1789.2011.01199.x",
    	issn = "1440-1789",
    	journal = "Neuropathology : official journal of the Japanese Society of Neuropathology",
    	keywords = "Biological Markers,Biological Markers: analysis,Humans,Immunohistochemistry,Inclusion Bodies,Inclusion Bodies: metabolism,Inclusion Bodies: pathology,Neurodegenerative Diseases,Neurodegenerative Diseases: metabolism,Neurodegenerative Diseases: pathology,Transcription Factor TFIIIA,Transcription Factor TFIIIA: analysis,Transcription Factor TFIIIA: metabolism",
    	month = "",
    	number = 6,
    	pages = "569--74",
    	pmid = 21284751,
    	title = "{Optineurin in neurodegenerative diseases.}",
    	url = "http://www.ncbi.nlm.nih.gov/pubmed/21284751",
    	volume = 31,
    	year = 2011
    }
    
  11. Tibor Hortobágyi, Claire Troakes, Agnes L Nishimura, Caroline Vance, John C Swieten, Harro Seelaar, Andrew King, Safa Al-Sarraj, Boris Rogelj and Christopher E Shaw.
    Optineurin inclusions occur in a minority of TDP-43 positive ALS and FTLD-TDP cases and are rarely observed in other neurodegenerative disorders.. Acta neuropathologica 121(4):519–27, 2011.
    Abstract Optineurin (OPTN) is a multifunctional protein involved in vesicular trafficking, signal transduction and gene expression. OPTN mutations were described in eight Japanese patients with familial and sporadic amyotrophic lateral sclerosis (FALS, SALS). OPTN-positive inclusions co-localising with TDP-43 were described in SALS and in FALS with SOD-1 mutations, potentially linking two pathologically distinct pathways of motor neuron degeneration. We have explored the abundance of OPTN inclusions using a range of antibodies in postmortem tissues from 138 cases and controls including sporadic and familial ALS, frontotemporal lobar degeneration (FTLD) and a wide range of neurodegenerative proteinopathies. OPTN-positive inclusions were uncommon and detected in only 11/32 (34%) of TDP-43-positive SALS spinal cord and 5/15 (33%) of FTLD-TDP. Western blot of lysates from FTLD-TDP frontal cortex and TDP-43-positive SALS spinal cord revealed decreased levels of OPTN protein compared to controls (p < 0.05), however, this correlated with decreased neuronal numbers in the brain. Large OPTN inclusions were not detected in FALS with SOD-1 and FUS mutation, respectively, or in FTLD-FUS cases. OPTN-positive inclusions were identified in a few Alzheimer's disease (AD) cases but did not co-localise with tau and TDP-43. Occasional striatal neurons contained granular cytoplasmic OPTN immunopositivity in Huntington's disease (HD) but were absent in spinocerebellar ataxia type 3. No OPTN inclusions were detected in FTLD-tau and $\alpha$-synucleinopathy. We conclude that OPTN inclusions are relatively rare and largely restricted to a minority of TDP-43 positive ALS and FTLD-TDP cases. Our results do not support the proposition that OPTN inclusions play a central role in the pathogenesis of ALS, FTLD or any other neurodegenerative disorder.
    URL, DOI BibTeX

    @article{Hortobagyi2011,
    	abstract = "Optineurin (OPTN) is a multifunctional protein involved in vesicular trafficking, signal transduction and gene expression. OPTN mutations were described in eight Japanese patients with familial and sporadic amyotrophic lateral sclerosis (FALS, SALS). OPTN-positive inclusions co-localising with TDP-43 were described in SALS and in FALS with SOD-1 mutations, potentially linking two pathologically distinct pathways of motor neuron degeneration. We have explored the abundance of OPTN inclusions using a range of antibodies in postmortem tissues from 138 cases and controls including sporadic and familial ALS, frontotemporal lobar degeneration (FTLD) and a wide range of neurodegenerative proteinopathies. OPTN-positive inclusions were uncommon and detected in only 11/32 (34\%) of TDP-43-positive SALS spinal cord and 5/15 (33\%) of FTLD-TDP. Western blot of lysates from FTLD-TDP frontal cortex and TDP-43-positive SALS spinal cord revealed decreased levels of OPTN protein compared to controls (p < 0.05), however, this correlated with decreased neuronal numbers in the brain. Large OPTN inclusions were not detected in FALS with SOD-1 and FUS mutation, respectively, or in FTLD-FUS cases. OPTN-positive inclusions were identified in a few Alzheimer's disease (AD) cases but did not co-localise with tau and TDP-43. Occasional striatal neurons contained granular cytoplasmic OPTN immunopositivity in Huntington's disease (HD) but were absent in spinocerebellar ataxia type 3. No OPTN inclusions were detected in FTLD-tau and $\alpha$-synucleinopathy. We conclude that OPTN inclusions are relatively rare and largely restricted to a minority of TDP-43 positive ALS and FTLD-TDP cases. Our results do not support the proposition that OPTN inclusions play a central role in the pathogenesis of ALS, FTLD or any other neurodegenerative disorder.",
    	author = "Hortob\'{a}gyi, Tibor and Troakes, Claire and Nishimura, Agnes L and Vance, Caroline and van Swieten, John C and Seelaar, Harro and King, Andrew and Al-Sarraj, Safa and Rogelj, Boris and Shaw, Christopher E",
    	doi = "10.1007/s00401-011-0813-3",
    	issn = "1432-0533",
    	journal = "Acta neuropathologica",
    	keywords = "Aged,Aged, 80 and over,Amyotrophic Lateral Sclerosis,Amyotrophic Lateral Sclerosis: pathology,Brain,Brain: pathology,DNA-Binding Proteins,DNA-Binding Proteins: metabolism,Female,Frontotemporal Lobar Degeneration,Frontotemporal Lobar Degeneration: pathology,Histamine Agonists,Histamine Agonists: metabolism,Humans,Indoles,Indoles: diagnostic use,Male,Middle Aged,Mutation,Mutation: genetics,Nerve Tissue Proteins,Nerve Tissue Proteins: metabolism,Neurons,Neurons: metabolism,Spinal Cord,Spinal Cord: pathology,Superoxide Dismutase,Superoxide Dismutase: genetics,Transcription Factor TFIIIA,Transcription Factor TFIIIA: genetics,Transcription Factor TFIIIA: metabolism,Tubulin,Tubulin: metabolism",
    	month = "",
    	number = 4,
    	pages = "519--27",
    	pmid = 21360076,
    	title = "{Optineurin inclusions occur in a minority of TDP-43 positive ALS and FTLD-TDP cases and are rarely observed in other neurodegenerative disorders.}",
    	url = "http://www.ncbi.nlm.nih.gov/pubmed/21360076",
    	volume = 121,
    	year = 2011
    }
    
  12. Han-Xiang Deng, Eileen H Bigio, Hong Zhai, Faisal Fecto, Kaouther Ajroud, Yong Shi, Jianhua Yan, Manjari Mishra, Senda Ajroud-Driss, Scott Heller, Robert Sufit, Nailah Siddique, Enrico Mugnaini and Teepu Siddique.
    Differential involvement of optineurin in amyotrophic lateral sclerosis with or without SOD1 mutations.. Archives of neurology 68(8):1057–61, 2011.
    Abstract BACKGROUND: Mutations in optineurin have recently been linked to amyotrophic lateral sclerosis (ALS). OBJECTIVE: To determine whether optineurin-positive skeinlike inclusions are a common pathologic feature in ALS, including SOD1 -linked ALS. DESIGN: Clinical case series. SETTING: Academic referral center. SUBJECTS: We analyzed spinal cord sections from 46 clinically and pathologically diagnosed ALS cases and ALS transgenic mouse models overexpressing ALS-linked SOD1 mutations G93A or L126Z. RESULTS: We observed optineurin-immunoreactive skeinlike inclusions in all the sporadic ALS and familial ALS cases without SOD1 mutation, but not in cases with SOD1 mutations or in transgenic mice overexpressing the ALS-linked SOD1 mutations G93A or L126Z. CONCLUSION: The data from this study provide evidence that optineurin is involved in the pathogenesis of sporadic ALS and non- SOD1 familial ALS, thus supporting the hypothesis that these forms of ALS share a pathway that is distinct from that of SOD1-linked ALS.
    URL, DOI BibTeX

    @article{Deng2011,
    	abstract = "BACKGROUND: Mutations in optineurin have recently been linked to amyotrophic lateral sclerosis (ALS). OBJECTIVE: To determine whether optineurin-positive skeinlike inclusions are a common pathologic feature in ALS, including SOD1 -linked ALS. DESIGN: Clinical case series. SETTING: Academic referral center. SUBJECTS: We analyzed spinal cord sections from 46 clinically and pathologically diagnosed ALS cases and ALS transgenic mouse models overexpressing ALS-linked SOD1 mutations G93A or L126Z. RESULTS: We observed optineurin-immunoreactive skeinlike inclusions in all the sporadic ALS and familial ALS cases without SOD1 mutation, but not in cases with SOD1 mutations or in transgenic mice overexpressing the ALS-linked SOD1 mutations G93A or L126Z. CONCLUSION: The data from this study provide evidence that optineurin is involved in the pathogenesis of sporadic ALS and non- SOD1 familial ALS, thus supporting the hypothesis that these forms of ALS share a pathway that is distinct from that of SOD1-linked ALS.",
    	author = "Deng, Han-Xiang and Bigio, Eileen H and Zhai, Hong and Fecto, Faisal and Ajroud, Kaouther and Shi, Yong and Yan, Jianhua and Mishra, Manjari and Ajroud-Driss, Senda and Heller, Scott and Sufit, Robert and Siddique, Nailah and Mugnaini, Enrico and Siddique, Teepu",
    	doi = "10.1001/archneurol.2011.178",
    	issn = "1538-3687",
    	journal = "Archives of neurology",
    	keywords = "Amyotrophic Lateral Sclerosis,Amyotrophic Lateral Sclerosis: genetics,Amyotrophic Lateral Sclerosis: metabolism,Amyotrophic Lateral Sclerosis: pathology,Animals,Diagnosis, Differential,Eye Proteins,Eye Proteins: genetics,Eye Proteins: metabolism,Genetic Markers,Genetic Markers: genetics,Genetic Predisposition to Disease,Genetic Predisposition to Disease: genetics,Humans,Mice,Mice, Transgenic,Neural Pathways,Neural Pathways: pathology,Superoxide Dismutase,Superoxide Dismutase: genetics,Transcription Factor TFIIIA,Transcription Factor TFIIIA: genetics,Transcription Factor TFIIIA: metabolism",
    	month = "",
    	number = 8,
    	pages = "1057--61",
    	pmid = 21825243,
    	title = "{Differential involvement of optineurin in amyotrophic lateral sclerosis with or without SOD1 mutations.}",
    	url = "http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3357952\&tool=pmcentrez\&rendertype=abstract",
    	volume = 68,
    	year = 2011
    }
    
  13. Ghanshyam Swarup and Ananthamurthy Nagabhushana.
    Optineurin, a multifunctional protein involved in glaucoma, amyotrophic lateral sclerosis and antiviral signalling.. Journal of biosciences 35(4):501–5, December 2010.
    URL BibTeX

    @article{Swarup2010,
    	author = "Swarup, Ghanshyam and Nagabhushana, Ananthamurthy",
    	issn = "0973-7138",
    	journal = "Journal of biosciences",
    	keywords = "Amyotrophic Lateral Sclerosis,Amyotrophic Lateral Sclerosis: metabolism,Cell Membrane,Cell Membrane: metabolism,Down-Regulation,Glaucoma,Glaucoma: metabolism,Humans,Interferon-beta,Interferon-beta: metabolism,Mutation,NF-kappa B,NF-kappa B: metabolism,Protein Structure, Tertiary,Protein Transport,RNA Virus Infections,RNA Virus Infections: metabolism,Signal Transduction,Transcription Factor TFIIIA,Transcription Factor TFIIIA: genetics,Transcription Factor TFIIIA: physiology,Ubiquitination",
    	month = "dec",
    	number = 4,
    	pages = "501--5",
    	pmid = 21289430,
    	title = "{Optineurin, a multifunctional protein involved in glaucoma, amyotrophic lateral sclerosis and antiviral signalling.}",
    	url = "http://www.ncbi.nlm.nih.gov/pubmed/21289430",
    	volume = 35,
    	year = 2010
    }
    
  14. Wataru Sako, Hidefumi Ito, Mari Yoshida, Hidetaka Koizumi, Masaki Kamada, Koji Fujita, Yoshio Hashizume, Yuishin Izumi and Ryuji Kaji.
    Nuclear factor $\kappa$ B expression in patients with sporadic amyotrophic lateral sclerosis and hereditary amyotrophic lateral sclerosis with optineurin mutations.. Clinical neuropathology 31(6):418–23.
    Abstract Nuclear factor $\kappa$ B (NF-$\kappa$B) is involved in the pathogenesis of a number of neurodegenerative disorders with neuroinflammation. In order to clarify the role of NF-$\kappa$B in ALS, immunohistochemical studies with an antibody that recognizes the p65 subunit of NF-$\kappa$B were performed on the spinal anterior horn of 4 patients with sporadic ALS (sALS), 1 patient with optineurin-mutated ALS (OPTN-ALS), and 3 normal controls (NC). In patients with sALS or OPTN-ALS, the expression pattern of NF-$\kappa$B was altered when compared to that of NC; NF-$\kappa$B immunoreactivity tended to be absent from neuronal nucleus and was increased in microglia. The down-regulation of NF-$\kappa$B in neuronal nucleus might contribute to a loss of neuroprotection, or neurons with nuclear NF-$\kappa$B might be lost immediately after its activation. The microglial induction of NF-$\kappa$B might contribute to neuroinflammation. In conclusion, NF-$\kappa$B signaling pathway could have a key role in the pathomechanism of ALS.
    URL, DOI BibTeX

    @article{Sako,
    	abstract = "Nuclear factor $\kappa$ B (NF-$\kappa$B) is involved in the pathogenesis of a number of neurodegenerative disorders with neuroinflammation. In order to clarify the role of NF-$\kappa$B in ALS, immunohistochemical studies with an antibody that recognizes the p65 subunit of NF-$\kappa$B were performed on the spinal anterior horn of 4 patients with sporadic ALS (sALS), 1 patient with optineurin-mutated ALS (OPTN-ALS), and 3 normal controls (NC). In patients with sALS or OPTN-ALS, the expression pattern of NF-$\kappa$B was altered when compared to that of NC; NF-$\kappa$B immunoreactivity tended to be absent from neuronal nucleus and was increased in microglia. The down-regulation of NF-$\kappa$B in neuronal nucleus might contribute to a loss of neuroprotection, or neurons with nuclear NF-$\kappa$B might be lost immediately after its activation. The microglial induction of NF-$\kappa$B might contribute to neuroinflammation. In conclusion, NF-$\kappa$B signaling pathway could have a key role in the pathomechanism of ALS.",
    	author = "Sako, Wataru and Ito, Hidefumi and Yoshida, Mari and Koizumi, Hidetaka and Kamada, Masaki and Fujita, Koji and Hashizume, Yoshio and Izumi, Yuishin and Kaji, Ryuji",
    	doi = "10.5414/NP300493",
    	issn = "0722-5091",
    	journal = "Clinical neuropathology",
    	keywords = "Aged,Aged, 80 and over,Amyotrophic Lateral Sclerosis,Amyotrophic Lateral Sclerosis: genetics,Amyotrophic Lateral Sclerosis: metabolism,Amyotrophic Lateral Sclerosis: pathology,Blotting, Western,Female,Humans,Immunohistochemistry,Male,Middle Aged,NF-kappa B,NF-kappa B: biosynthesis,Spinal Cord,Spinal Cord: metabolism,Spinal Cord: pathology,Transcription Factor TFIIIA,Transcription Factor TFIIIA: genetics",
    	number = 6,
    	pages = "418--23",
    	pmid = 22762947,
    	title = "{Nuclear factor $\kappa$ B expression in patients with sporadic amyotrophic lateral sclerosis and hereditary amyotrophic lateral sclerosis with optineurin mutations.}",
    	url = "http://www.ncbi.nlm.nih.gov/pubmed/22762947",
    	volume = 31
    }