Abstract
A single paragraph of about 200 words maximum. Neurodegenerative diseases (ND), such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, pose a global challenge in the aging population due to the lack of treatments for their cure. Despite various disease-specific clinical symptoms, ND have some fundamental common pathological mechanisms involving oxidative stress and neuroinflammation. The present review focuses on the major causes of central nervous system (CNS) redox homeostasis imbalance comprising mitochondrial dysfunction and endoplasmic reticulum (ER) stress. Mitochondrial disturbances, leading to reduced mitochondrial function and elevated reactive oxygen species (ROS) production, are thought to be a major contributor to the pathogenesis of ND. ER dysfunction has been implicated in ND in which protein misfolding evidently causes ER stress. The consequences of ER stress ranges from an increase in ROS production to altered calcium efflux and proinflammatory signaling in glial cells. Both pathological pathways have links to ferroptotic cell death, which has been implicated to play an important role in ND. Pharmacological targeting of these pathological pathways may help alleviate or slow down neurodegeneration.
Highlights
Received: 8 January 2022Redox homeostasis is acknowledged to play a major role in both normal cellular function and disease of the human central nervous system (CNS)
Since neurons rely on oxidative phosphorylation as the main energy source, mitochondrial function is of utmost importance in studies relating to Neurodegenerative diseases (ND)
endoplasmic reticulum (ER) stress induced in microglia and resulting in their neuroinflammatory phenotype has been implicated for the decrease in neural stem cells in an animal model of paraquat exposure [61]
Summary
Redox homeostasis is acknowledged to play a major role in both normal cellular function and disease of the human central nervous system (CNS). This review aims to cover several major intracellular pathways affecting redox homeostasis and being relevant in the scope of degenerative diseases of the CNS. We reveal several important linking axes between the pathways of mitochondrial reactive oxygen species (ROS) production and ferroptosis, and oxidative protein refolding in endoplasmic reticulum (ER) and neuroinflammation. We discuss the relevance of these pathways in the pathogenesis of several NDs, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease. Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations
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