Progress on the mechanism of PERK in neurodegene-rative diseases

doi:10.3877/cma.j.issn.2095-123X.2025.05.008

Abstract

Abstract:

Protein kinase R-like endoplasmic reticulum kinase (PERK) can regulate the inactivation of the eukaryotic initiation factor 2 signalling cascade in response to cellular stress. Cellular and endoplasmic reticulum (ER) stress activates the unfolded protein response (UPR) signalling pathway, and ER dysfunction leads to abnormal protein folding and aggregation, causing synaptic and neuronal dysfunction. Abnormal protein aggregation induces an ER stress state, promoting the UPR to shift towards apoptosis, resulting in neurodegeneration. The mitochondrial membrane is connected to the ER membrane, and ER stress activates PERK to regulate mitochondrial dynamics adaptation; PERK activation induces mitochondrial fusion; PERK activation increases the formation of mitochondrial cristae and respiratory chain complexes. Mitochondrial damage and oxidative stress are closely related to the pathogenesis of neurodegene-rative diseases such as Alzheimer disease, Parkinson disease, Huntington disease, and multiple sclerosis. This article reviews the mechanisms of PERK in neurodegene-rative diseases, aiming to provide theoretical basis for the treatment of neurodegene-rative diseases.

Key words: Protein kinase R-like endoplasmic reticulum kinase, Neurodegene-rative disease, Endoplasmic reticulum stress, Unfolded protein response, Mitochondria

Tao Xu, Lirong Zhang, Hongqiang Lian. Progress on the mechanism of PERK in neurodegene-rative diseases[J]. Chinese Journal of Brain Diseases and Rehabilitation(Electronic Edition), 2025, 15(05): 298-302.

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References 34

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