Peroxisomal Dysfunction and Oxidative Stress in Neurodegenerative Disease: A Bidirectional Crosstalk

Abstract

Peroxisomes are multifunctional organelles best known for their role in cellular lipid and hydrogen peroxide metabolism. In this chapter, we review and discuss the diverse functions of this organelle in brain physiology and neurodegeneration, with a particular focus on oxidative stress. We first briefly summarize what is known about the various nexuses between peroxisomes, the central nervous system, oxidative stress, and neurodegenerative disease. Next, we provide a comprehensive overview of the complex interplay between peroxisomes, oxidative stress, and neurodegeneration in patients suffering from primary peroxisomal disorders. Particular examples that are discussed include the prototypic Zellweger spectrum disorders and X-linked adrenoleukodystrophy, the most prevalent peroxisomal disorder. Thereafter, we elaborate on secondary peroxisome dysfunction in more common neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Finally, we highlight some issues and challenges that need to be addressed to progress towards therapies and prevention strategies preserving, normalizing, or improving peroxisome activity in patients suffering from neurodegenerative conditions.

Effect of Butylphthalide soft capsules on cognitive function and dementia-related factors in elderly patients with Parkinson’s disease dementia during the COVID-19 pandemic

“…Most patients with PDD have different degrees of free radical clearance disturbance in the brain tissue, mainly manifested as increased lipid peroxidation substances such as MDA, and decreased activity of antioxidant enzymes such as CAT, GSH-Px, and SOD. These further aggravate dopaminergic neuron damage and induce a series of dementia symptoms [25]. Neurotrophic factors such as GDNF, BDNF, and NGF have been confirmed to participate in the pathogenesis of various neurodegenerative diseases, and the mechanism of action is that neurotrophic factors promote the growth of neurons mainly by binding to tyrosine kinase receptors to activate downstream signaling pathways [26].…”

Neurons undergo pathogenic metabolic reprogramming in models of familial ALS

“…Oxidative stress is a cardinal feature of neurodegenerative disease in general [ 90 , 91 ] and ALS specifically [ 92 ] and direct targeting of reactive oxygen species (ROS) generation systems has been repeatedly shown to confer benefits in model systems [ 15 , 93 ]. The potent antioxidant Edaravone is one of two Food and Drug Administration approved medications for ALS [ 94 ].…”

NRF2 Activation and Downstream Effects: Focus on Parkinson’s Disease and Brain Angiotensin

“…Peroxisomes also use molecular oxygen as a key reactive component of their normal metabolic functions. Peroxisomes contain several oxidative enzymes that result in hydrogen peroxide production, as well as catalase, an enzyme that, under non-pathological conditions, is able to decompose hydrogen peroxide into water and oxygen [ 8 ]. The endoplasmic reticulum is another source of ROS, derived from reactions required for protein folding or from NADPH oxidase (NOX) isoforms found in the endoplasmic reticulum [ 9 ].…”