https://www.sciencedirect.com/science/article/abs/pii/S0014299920306786?via%3Dihub
https://www.ncbi.nlm.nih.gov/pubmed/32971086?dopt=Abstract
TITLE:
Asparagine endopeptidase inhibitor protects against fenpropathrin-induced neurodegeneration via suppressing α-synuclein aggregation and neuroinflammation.
DESCRIPTION:
Asparagine endopeptidase inhibitor protects against fenpropathrin-induced neurodegeneration via suppressing α-synuclein aggregation and neuroinflammation.
Eur J Pharmacol. 2020 Sep 21;:173586
Authors: Yu T, Wan F, Liu C, Zhang X, Liu Z, Zhang J, Xiong J, Wang T, Zhang Z
Abstract
Exposure to fenpropathrin (Fen), one of the most widely used pyrethroid pesticides, has been reported to increase the incidence of Parkinson’s disease (PD). However, the molecular mechanisms underlying Fen-induced Parkinsonism remain unknown. Here we investigated the role of the lysosomal protease asparagine endopeptidase (AEP) in Fen-induced neurodegeneration and tested the protective effect of an AEP inhibitor Compound #11 (CP11). Fen induced AEP activation, α-synuclein aggregation, and dopaminergic neuronal degeneration both in vitro and in vivo. CP11 alleviated Fen-induced cell injury in cultured SH-SY5Y cells and A53T α-synuclein transgenic mice. CP11 protected SH-SY5Y cells against Fen-induced toxicity and decreased α-synuclein aggregation in HEK293 cells stably transfected with α-synuclein. In Fen-treated mice, CP11 attenuated the degeneration of dopaminergic neurons and reduced neuroinflammation. Our findings demonstrate that neurodegeneration in Fen-treated models might be attributed to the activation of AEP. AEP might be a novel therapeutic target in PD induced by Fen and other environmental factors.
PMID: 32971086 [PubMed – as supplied by publisher]
PMID:
PubMed:32971086
DATE FOUND:
09/25/20 06:01AM
LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/32971086?dopt=Abstract