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PKC Delta Activation Promotes Endoplasmic Reticulum Stress (ERS) and NLR Family Pyrin Domain-Containing 3 (NLRP3) Inflammasome Activation Subsequent to Asynuclein-Induced Microglial Activation: Involvement of Thioredoxin-Interacting Protein (TXNIP)/Thioredoxin (Trx) Redoxisome Pathway

Front Aging Neurosci. 2021-07; 
Manikandan Samidurai, Bharathi N Palanisamy, Alejandra Bargues-Carot, Monica Hepker, Naveen Kondru, Sireesha Manne, Gary Zenitsky, Huajun Jin, Vellareddy Anantharam, Anumantha G Kanthasamy, Arthi Kanthasamy
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摘要

A classical hallmark of Parkinson's disease (PD) pathogenesis is the accumulation of misfolded alpha-synuclein (αSyn) within Lewy bodies and Lewy neurites, although its role in microglial dysfunction and resultant dopaminergic (DAergic) neurotoxicity is still elusive. Previously, we identified that protein kinase C delta (PKCδ) is activated in post mortem PD brains and experimental Parkinsonism and that it participates in reactive microgliosis; however, the relationship between PKCδ activation, endoplasmic reticulum stress (ERS) and the reactive microglial activation state in the context of α-synucleinopathy is largely unknown. Herein, we show that oxidative stress, mitochondrial dysfunction, NLR family pyr... More

关键词

ER stress, NLRP3, PKCδ, Parkinson’s disease, TXNIP