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

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 oxida-tive stress. We first briefly summarize what is known about the vari-ous nexuses between peroxisomes, the central nervous system, oxi-dative stress, and neurodegenerative disease. Next, we provide a comprehensive overview of the complex interplay between peroxi-somes, oxidative stress, and neurodegeneration in patients suffering from primary peroxisomal disorders. Particular examples that are dis-cussed include the prototypic Zellweger spectrum disorders and X-linked adrenoleukodystrophy, the most prevalent peroxisomal disor-der. Thereafter, we elaborate on secondary peroxisome dysfunction in more common neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. Finally, we high-light some issues and challenges that need to be addressed to pro-gress towards therapies and prevention strategies preserving, normal-izing, or improving peroxisome activity in patients suffering from neurodegenerative conditions.status: publishe