RT Journal Article
SR Electronic
T1 Amyloid Precursor Protein, Presenilins, and α-Synuclein: Molecular Pathogenesis and Pharmacological Applications in Alzheimer's Disease
JF Pharmacological Reviews
JO Pharmacol Rev
FD American Society for Pharmacology and Experimental Therapeutics
SP 469
OP 525
DO 10.1124/pr.54.3.469
VO 54
IS 3
A1 Suh, Yoo-Hun
A1 Checler, Frederic
YR 2002
UL http://pharmrev.aspetjournals.org/content/54/3/469.abstract
AB Alzheimer's disease (AD) is the most common cause of dementia that arises on a neuropathological background of amyloid plaques containing β-amyloid (Aβ) derived from amyloid precursor protein (APP) and τ-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 Aβ 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 Aβ and α-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 Aβ, presenilins, and/or α-synuclein. Therefore, treatments that block the accumulation of Aβ and α-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 α-synuclein, their interactions, and therapeutic strategies for AD.