title: Bcl11b: A New Piece to the Complex Puzzle of Amyotrophic Lateral Sclerosis Neuropathogenesis?
abstract: Amyotrophic lateral sclerosis (ALS) is an idiopathic, fatal, neurodegenerative disease of the human motor system. The pathogenesis of ALS is a topic of fascinating speculation and experimentation, with theories revolving around intracellular protein inclusions, mitochondrial structural issues, glutamate excitotoxicity and free radical formation. This review explores the rationale for the involvement of a novel protein, B-cell lymphoma/leukaemia 11b (Bcl11b) in ALS. Bcl11b is a multifunctional zinc finger protein transcription factor. It functions as both a transactivator and genetic suppressor, acting both directly, binding to promoter regions, and indirectly, binding to promoter-bound transcription factors. It has essential roles in the differentiation and growth of various cells in the central nervous system, immune system, integumentary system and cardiovascular system, to the extent that Bcl11b knockout mice are incompatible with extra-uterine life. It also has various roles in pathology including the suppression of latent retroviruses, thymic tumourigenesis and neurodegeneration. In particular its functions in neurodevelopment, viral latency and T-cell development suggest potential roles in ALS pathology.
authors.affiliation: Peter Duncan Neurosciences Research Unit, St Vincent's Centre for Applied Medical Research, Sydney, Australia.|Faculty of Medicine, University of New South Wales, Sydney, Australia.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Lennon
authors.affiliation: Peter Duncan Neurosciences Research Unit, St Vincent's Centre for Applied Medical Research, Sydney, Australia.|Faculty of Medicine, University of New South Wales, Sydney, Australia.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Jones
authors.affiliation: Peter Duncan Neurosciences Research Unit, St Vincent's Centre for Applied Medical Research, Sydney, Australia.|Faculty of Medicine, University of New South Wales, Sydney, Australia.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Lovelace
authors.affiliation: Faculty of Medicine and Health Sciences, MND Research Centre, Macquarie University, Sydney, Australia.
authors.forename: Gilles J
authors.initials: GJ
authors.lastname: Guillemin
authors.affiliation: Peter Duncan Neurosciences Research Unit, St Vincent's Centre for Applied Medical Research, Sydney, Australia. B.Brew@unsw.edu.au.|Faculty of Medicine, University of New South Wales, Sydney, Australia. B.Brew@unsw.edu.au.|Department of Neurology, St Vincent's Hospital, Level 4 Xavier Building, Victoria Street, Darlinghurst, Sydney, NSW, 2010, Australia. B.Brew@unsw.edu.au.
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Brew
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D004660:Encephalitis / Q000235:genetics / Q000378:metabolism; D020077:Endogenous Retroviruses / Q000378:metabolism; D006801:Humans; D051379:Mice; D009046:Motor Neurons / Q000378:metabolism; D009416:Nerve Regeneration; D009474:Neurons / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C479740:BCL11B protein, human; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins
keywords: Amyotrophic lateral sclerosis; Bcl11b; Motor neurone disease; Neurodegeneration; Neuroinflammation; Transcription factor; Viral latency