title: RNAi silencing in mouse models of neurodegenerative diseases.
abstract: RNA interference (RNAi) has emerged as a potential therapeutic approach for neurodegenerative diseases, particularly those associated with autosomal dominant patterns of inheritance. In proof of concept experiments, several groups have demonstrated efficacy of using viral vectors expressing short hairpin RNA (shRNA) directed against therapeutically relevant genes in mouse models of neurodegenerative diseases, including spinocerebellar ataxia, Amyotrophic Lateral Sclerosis, Huntington's Disease and amyloidosis (a pathological aspect of Alzheimer's Disease). Although viral-based RNAi has limitations that most likely will preclude its usage in humans, a few recent developments underscore the potential of non-viral-based delivery of relevant RNAi as therapeutics for neurodegenerative diseases. Here, I will review the recent literature on effectiveness of RNAi as a therapeutic strategy in mouse models of neurodegenerative diseases.
authors: Division of Neuropathology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA. mfarah2@jhem.jhmi.edu
authors: Mohamed H
authors: MH
authors: Farah
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism; D000686:Amyloidosis / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism; D000067696:Ataxin-1; D000067528:Ataxins; D001812:Blood-Brain Barrier; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000096:biosynthesis* / Q000235:genetics; D020754:Spinocerebellar Ataxias / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1
chemical_list: C000593749:ATXN1 protein, human; D000067696:Ataxin-1; D000067528:Ataxins; C000593750:Atxn1 protein, mouse; C506812:Htt protein, mouse; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering; C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse