Autophagy and exosomes; inter-connected maestros in Alzheimer's disease.

Autor: Atya HB; Biochemistry and Molecular Biology Department, Faculty of Pharmacy, Helwan University, P.O. Box 11795, Cairo, Egypt. hanaa.atya@pharm.helwan.edu.eg., Sharaf NM; Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, German University in Cairo-(GUC), Cairo, Egypt., Abdelghany RM; Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, German University in Cairo-(GUC), Cairo, Egypt., El-Helaly SN; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt., Taha H; Biochemistry and Molecular Biology Department, Faculty of Pharmacy, Helwan University, P.O. Box 11795, Cairo, Egypt.
Jazyk: angličtina
Zdroj: Inflammopharmacology [Inflammopharmacology] 2024 Jun; Vol. 32 (3), pp. 2061-2073. Date of Electronic Publication: 2024 Apr 02.
DOI: 10.1007/s10787-024-01466-3
Abstrakt: Autophagy is a crucial process involved in the degradation and recycling of cytoplasmic components which are transported to the lysosomal compartment by autophagosomes. Exosomes are an important means of communication and signaling in both normal and diseased states, and they have a significant role in the transmission and propagation of proteins, especially proteins implicated in neurodegenerative disorders. Autophagy may affect exosomal processing, but whether autophagy controls the release of aggregated β-amyloid and tau proteins in exosomes of Alzheimer disease (AD) is unclear. Therefore, our study aimed to investigate how modulating autophagy affects the exosomal release of these proteins in animal models of AD. Isolated exosomes from brain tissues of 48 male albino mice were divided into four groups (Negative control, LPS, rapamycin (RAPA), and chloroquine (CQ). LC3 I and LC3 II as well as Aβ and Tau proteins levels were determined. All mice undergone Neuro-behavioral tests (Morris Water maze test, Y-maze test, and Novel Object Recognition). Both LPS and CQ groups showed reduced expression levels of LC3 II and LC3 II/LC3 I ratio. In contrast, RAPA group showed a significant increase in both LC3-II expression and LC3-II/LC3-I ratio. The levels of both Aβ & Tau in exosomes of CQ & LPS groups were higher. While RAPA group showed a significant diminished levels of tau & Aβ proteins. In conclusion, our findings suggest that autophagy alterations in AD can influence the release of Aβ and tau proteins through exosomes, which may impact the spread of misfolded proteins in AD. These results highlight a potential innovative therapeutic approach for combating AD.
(© 2024. The Author(s).)
Databáze: MEDLINE
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