Amyloid β precursor protein as a molecular target for amyloid β--induced neuronal degeneration in Alzheimer's disease.

Autor: Bignante EA; Laboratory of Experimental Neuropathology, Instituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC-CONICET, Universidad Nacional de Córdoba, 5016 Córdoba, Argentina., Heredia F, Morfini G, Lorenzo A
Jazyk: angličtina
Zdroj: Neurobiology of aging [Neurobiol Aging] 2013 Nov; Vol. 34 (11), pp. 2525-37. Date of Electronic Publication: 2013 May 25.
DOI: 10.1016/j.neurobiolaging.2013.04.021
Abstrakt: A role of amyloid β (Aβ) peptide aggregation and deposition in Alzheimer's disease (AD) pathogenesis is widely accepted. Significantly, abnormalities induced by aggregated Aβ have been linked to synaptic and neuritic degeneration, consistent with the "dying-back" pattern of degeneration that characterizes neurons affected in AD. However, molecular mechanisms underlying the toxic effect of aggregated Aβ remain elusive. In the last 2 decades, a variety of aggregated Aβ species have been identified and their toxic properties demonstrated in diverse experimental systems. Concurrently, specific Aβ assemblies have been shown to interact and misregulate a growing number of molecular effectors with diverse physiological functions. Such pleiotropic effects of aggregated Aβ posit a mayor challenge for the identification of the most cardinal Aβ effectors relevant to AD pathology. In this review, we discuss recent experimental evidence implicating amyloid β precursor protein (APP) as a molecular target for toxic Aβ assemblies. Based on a significant body of pathologic observations and experimental evidence, we propose a novel pathologic feed-forward mechanism linking Aβ aggregation to abnormalities in APP processing and function, which in turn would trigger the progressive loss of neuronal connectivity observed early in AD.
(Copyright © 2013 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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