The Molecular Mechanisms of Neuroinflammation in Alzheimer's Disease, the Consequence of Neural Cell Death

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Jul 29

PMID 37511515

Authors

Su-Bin Choi

Sehee Kwon

Ji-Hye Kim

Na-Hyun Ahn

Joo-Hee Lee

Seung-Hoon Yang

Affiliations

Soon will be listed here.

Abstract

Alzheimer's disease (AD) is accompanied by neural cell loss and memory deficit. Neural cell death, occurring via apoptosis and autophagy, is widely observed in the AD brain in addition to neuroinflammation mediated by necroptosis and the NLRP3 inflammasome. Neurotoxicity induced by amyloid-beta (Aβ) and tau aggregates leads to excessive neural cell death and neuroinflammation in the AD brain. During AD progression, uncontrolled neural cell death results in the dysregulation of cellular activity and synaptic function. Apoptosis mediated by pro-apoptotic caspases, autophagy regulated by autophagy-related proteins, and necroptosis controlled by the RIPK/MLKL axis are representative of neural cell death occurred during AD. Necroptosis causes the release of cellular components, contributing to the pro-inflammatory environment in the AD brain. Inordinately high levels of neural cell death and pro-inflammatory events lead to the production of pro-inflammatory cytokines and feed-forward hyper neuroinflammation. Thus, neural cell death and neuroinflammation cause synaptic dysfunction and memory deficits in the AD brain. In this review, we briefly introduce the mechanisms of neural cell death and neuroinflammation observed in the AD brain. Combined with a typical strategy for targeting Aβ and tau, regulation of neural cell death and neuroinflammation may be effective for the amelioration of AD pathologies.

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