Endosomal dysfunction impacts extracellular vesicle release: Central role in Aβ pathology.

Autor: Arbo BD; Departmento de Farmacologia, Instituto de Ciências Básicas da Saúde (ICBS), Rua Sarmento Leite, 500 (90050-170), Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Ciências Fisiológicas, Universidade Federal do Rio Grande (FURG), Av. Itália, km. 8 (96203-900), Rio Grande, RS, Brazil; Programa de Pós-Graduação em Ciências Biológicas: Farmacologia e Terapêutica, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Sarmento Leite, 500 (90050-170), Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Ciências Biológicas: Fisiologia, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Sarmento Leite, 500 (90050-170), Porto Alegre, RS, Brazil. Electronic address: brunoarbo@gmail.com., Cechinel LR; Programa de Pós-Graduação em Ciências Biológicas: Fisiologia, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Sarmento Leite, 500 (90050-170), Porto Alegre, RS, Brazil., Palazzo RP; Programa de Pós-Graduação em Ciências Biológicas: Farmacologia e Terapêutica, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Sarmento Leite, 500 (90050-170), Porto Alegre, RS, Brazil., Siqueira IR; Departmento de Farmacologia, Instituto de Ciências Básicas da Saúde (ICBS), Rua Sarmento Leite, 500 (90050-170), Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Ciências Biológicas: Farmacologia e Terapêutica, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Sarmento Leite, 500 (90050-170), Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Ciências Biológicas: Fisiologia, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Sarmento Leite, 500 (90050-170), Porto Alegre, RS, Brazil.
Jazyk: angličtina
Zdroj: Ageing research reviews [Ageing Res Rev] 2020 Mar; Vol. 58, pp. 101006. Date of Electronic Publication: 2019 Dec 28.
DOI: 10.1016/j.arr.2019.101006
Abstrakt: Alzheimer's Disease (AD) is characterized by progressive loss of cognitive abilities; senile plaques represent the major histopathological findings. Amyloid precursor protein (APP) processing machinery, and its product amyloid-beta (Aβ) peptide, have been found in extracellular vesicles (EVs), specifically exosomes, which allows for Aβ peptide aggregation and subsequent senile plaques deposition. We review the APP processing imbalance in EVs, autophagic and endosomal pathways in AD. Increased intraluminal vesicle (ILV) production and exosome release appear to counteract the endosomal dysfunction of APP processing; however, this process results in elevated amyloidogenic processing of APP and augmented senile plaque deposition. Several players related to APP processing and dysfunctional endosomal-lysosomal-exosomal (and other EVs) pathway are described, and the interconnected systems are discussed. The components Arc, p75, Rab11 and retromer complex emerge as candidates for key convergent mechanisms that lead to increased EVs loaded with APP machinery and Aβ levels, in atrophy and damage of basal forebrain cholinergic neurons in AD.
Competing Interests: Declaration of Competing Interest None.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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