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

NEUROBIOLOGY OF AGING

卷:34

Review

Bignante, Elena Anahi¹  Heredia, Florencia¹  Morfini, Gerardo²  Lorenzo, Alfredo^1,3 

[1] Univ Nacl Cordoba, INIMEC CONICET, Inst Invest Med Mercedes & Martin Ferreyra, Expt Neuropathol Lab, RA-5016 Cordoba, Argentina

[2] Univ Illinois, Dept Anat & Cell Biol, Chicago, IL USA

[3] Univ Nacl Cordoba, Fac Ciencias Quim, Dept Farmacol, RA-5000 Cordoba, Argentina

关键词: APP;    Alzheimer's disease;    A beta;    Neuritic dystrophy;    Synaptic degeneration;    Dying-back degeneration;   

DOI  :  10.1016/j.neurobiolaging.2013.04.021

来源: Elsevier

【 摘 要 】

A role of amyloid beta (A beta) peptide aggregation and deposition in Alzheimer's disease (AD) pathogenesis is widely accepted. Significantly, abnormalities induced by aggregated A beta 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 A beta remain elusive. In the last 2 decades, a variety of aggregated A beta species have been identified and their toxic properties demonstrated in diverse experimental systems. Concurrently, specific A beta assemblies have been shown to interact and misregulate a growing number of molecular effectors with diverse physiological functions. Such pleiotropic effects of aggregated A beta posit a mayor challenge for the identification of the most cardinal A beta effectors relevant to AD pathology. In this review, we discuss recent experimental evidence implicating amyloid beta precursor protein (APP) as a molecular target for toxic A beta assemblies. Based on a significant body of pathologic observations and experimental evidence, we propose a novel pathologic feed-forward mechanism linking A beta aggregation to abnormalities in APP processing and function, which in turn would trigger the progressive loss of neuronal connectivity observed early in AD. (C) 2013 Elsevier Inc. All rights reserved.

【 授权许可】

Free