title: [RNAi and neurological disease].
abstract: In many of autosomal dominant diseases such as familial amyotrophic lateral sclerosis (ALS) with Cu/Zn superoxide dismutase (SOD1) mutation, a missense point mutation may induce the disease by its gain of adverse property. Similar 'gain of toxic function' of mutant protein is predicted to cause cell death in other autosomal dominant neurodegenerative diseases such as familial Alzheimer disease, prion disease, polyglutamine diseases and Parkinson disease. In all these familial diseases, one rational approach to therapy is to develop a method to specifically eliminate the aberrant protein. Duplex of 21-nt RNA, known as siRNA, has recently emerged as a powerful tool to silence gene. Mutant-allele specific gene silencing with siRNA was showed in familial ALS and Machado-Joseph diseases. We made the transgenic (Tg) mouse of modified small interfering RNA (siRNA). By crossing this anti-SOD1 siRNA Tg mouse with a SOD1(G93A) Tg mouse as a model for ALS, siRNA halted the development of disease by inhibiting mutant G93A SOD1. Our results support the feasibility of utilizing siRNA-based gene therapy of neurodegenerative diseases of autosomal dominant inheritance.
authors.affiliation: Department of Neurology and Neurological Science, Tokyo Medical and Dental University.
authors.forename: Takanori
authors.initials: T
authors.lastname: Yokota
mesh_terms: D000690:Amyotrophic Lateral Sclerosis; D000818:Animals; D015316:Genetic Therapy; D051379:Mice; D008822:Mice, Transgenic; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000628:therapy*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000627:therapeutic use; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1
chemical_list: D034741:RNA, Small Interfering; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1