期刊
ADVANCED DRUG DELIVERY REVIEWS
卷 59, 期 11, 页码 1093-1102出版社
ELSEVIER
DOI: 10.1016/j.addr.2007.08.013
关键词
transgenic; models; neurodegenerative disease; aging; Alzheimer's; Parkinson's; lewy bodies; MSA
资金
- NIA NIH HHS [AG5131, AG18440, AG10435, AG11385] Funding Source: Medline
- NINDS NIH HHS [NS44233] Funding Source: Medline
Neurodegenerative disorders of the aging population affect over 5 million people in the US and Europe alone. The common feature is the progressive accumulation of misfolded proteins with the formation of toxic oligomers. Previous studies show that while in Alzheimer's disease (AD) inisfolded amyloid-beta protein accumulates both in the intracellular and extracellular space, in Lewy body disease (LBD), Parkinson's disease (PD), Multiple System Atrophy (MSA), Fronto-Temporal dementia (FTD), prion diseases, amyotrophic lateral sclerosis (ALS) and trinucleotide repeat disorders (TNRD), the aggregated proteins accumulate in the plasma membrane and intracellularly. Protein misfolding and accumulation is the result of an altered balance between protein synthesis, aggregation rate and clearance. Based on these studies, considerable advances have been made in the past years in developing novel experimental models of neurodegenerative disorders. This has been in part driven by the identification of genetic mutations associated with familial forms of these conditions and gene polymorphisms associated with the more cornmon sporadic variants of these diseases. Transgenic and knock out rodents and Drosophila as well as viral vector driven models of Alzheimer's disease (AD), PD, Huntington's disease (HD) and others have been developed, however the focus for this review will be on rodent models of AD, FTD, PD/LBD, and MSA. Promising therapeutic results have been obtained utilizing arnyloid precursor protein (APP) transgenic (tg) models of AD to develop therapies including use of inhibitors of the APP-processing enzymes beta- and -gamma-secretase as well as vaccine therapies. (C) 2007 Published by Elsevier B.V.
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