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Neurodegenerative diseases: a decade of discoveries paves the way for therapeutic breakthroughs
Authors:Forman Mark S  Trojanowski John Q  Lee Virginia M-Y
Institution:Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Institute on Aging, University of Pennsylvania, 36th and Spruce Streets, Maloney Building, 3rd Floor, Philadelphia, Pennsylvania 19104-4283, USA.
Abstract:A wide variety of neurodegenerative diseases are characterized by the accumulation of intracellular or extracellular protein aggregates. More recently, the genetic identification of mutations in familial counterparts to the sporadic disorders, leading to the development of in vitro and in vivo model systems, has provided insights into disease pathogenesis. The effect of many of these mutations is the abnormal processing of misfolded proteins that overwhelms the quality-control systems of the cell, resulting in the deposition of protein aggregates in the nucleus, cytosol and/or extracellular space. Further understanding of mechanisms regulating protein processing and aggregation, as well as of the toxic effects of misfolded neurodegenerative disease proteins, will facilitate development of rationally designed therapies to treat and prevent these disorders.
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