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Review ArticleReview

Amyloid Precursor Protein, Presenilins, and α-Synuclein: Molecular Pathogenesis and Pharmacological Applications in Alzheimer's Disease

Yoo-Hun Suh and Frederic Checler
Pharmacological Reviews September 2002, 54 (3) 469-525; DOI: https://doi.org/10.1124/pr.54.3.469
Yoo-Hun Suh
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Frederic Checler
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This article has a correction. Please see:

  • Correction to “Amyloid Precursor Protein, Presenilins, and α-Synuclein: Molecular Pathogenesis and Pharmacological Applications in Alzheimer's Disease” - June 01, 2006

Abstract

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.

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Pharmacological Reviews: 54 (3)
Pharmacological Reviews
Vol. 54, Issue 3
1 Sep 2002
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Review ArticleReview

Amyloid Precursor Protein, Presenilins, and α-Synuclein: Molecular Pathogenesis and Pharmacological Applications in Alzheimer's Disease

Yoo-Hun Suh and Frederic Checler
Pharmacological Reviews September 1, 2002, 54 (3) 469-525; DOI: https://doi.org/10.1124/pr.54.3.469

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Review ArticleReview

Amyloid Precursor Protein, Presenilins, and α-Synuclein: Molecular Pathogenesis and Pharmacological Applications in Alzheimer's Disease

Yoo-Hun Suh and Frederic Checler
Pharmacological Reviews September 1, 2002, 54 (3) 469-525; DOI: https://doi.org/10.1124/pr.54.3.469
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  • Article
    • Abstract
    • I. Introduction
    • II. Amyloid Precursor Protein
    • III. Presenilin
    • IV. α-Synuclein
    • V. Therapeutic Targets for Alzheimer's Disease
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