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Pharmacol Rev. 2002 Sep;54(3):469-525.

Amyloid precursor protein, presenilins, and alpha-synuclein: molecular pathogenesis and pharmacological applications in Alzheimer's disease.

Author information

1
Department of Pharmacology, College of Medicine, National Creative Research Initiative Center for Alzheimer's Dementia and Neuroscience Research Institute, MRC, Seoul National University, Seoul, South Korea. yhsun@plaza.snu.ac.kr

Erratum in

  • Pharmacol Rev. 2006 Jun;58(2):280.

Abstract

Alzheimer's disease (AD) is the most common cause of dementia that arises on a neuropathological background of amyloid plaques containing beta-amyloid (A beta) derived from amyloid precursor protein (APP) and tau-rich neurofibrillary tangles. To date, the cause and progression of both familial and sporadic AD have not been fully elucidated. The autosomal-dominant inherited forms of early-onset Alzheimer's disease are caused by mutations in the genes encoding APP, presenilin-1 (chromosome 14), and presenilin-2 (chromosome 1). APP is processed by several different proteases such as secretases and/or caspases to yield A beta and carboxyl-terminal fragments, which have been implicated in the pathogenesis of Alzheimer's disease. Alzheimer's disease and Parkinson's disease are associated with the cerebral accumulation of A beta and alpha-synuclein, respectively. Some patients have clinical and pathological features of both diseases, raising the possibility of overlapping pathogenic pathways. Recent studies have strongly suggested the possible pathogenic interactions between A beta, presenilins, and/or alpha-synuclein. Therefore, treatments that block the accumulation of A beta and alpha-synuclein might benefit a broad spectrum of neurodegenerative disorders. This review covers the trafficking and processing of APP, amyloid cascade hypothesis in AD pathogenesis, physiological and pathological roles of presenilins, molecular characteristics of alpha-synuclein, their interactions, and therapeutic strategies for AD.

PMID:
12223532
[Indexed for MEDLINE]

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