Role of peroxisome proliferator-activated receptor alpha in neurodegenerative diseases and other neurological disorders: Clinical application prospects

Peroxisome proliferator-activated receptor alpha is a member of the nuclear hormone receptor superfamily and functions as a transcription factor involved in regulating cellular metabolism. Previous studies have shown that PPARα plays a key role in the onset and progression of neurodegenerative disea...

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Main Authors: Zijun Wu, Yuying Zhao, Shujing Hao, Mengyao An, Chengcheng Song, Jing Li
Format: Article
Language:English
Published: Wolters Kluwer Medknow Publications 2026-04-01
Series:Neural Regeneration Research
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Online Access:https://journals.lww.com/10.4103/NRR.NRR-D-24-01371
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author Zijun Wu
Yuying Zhao
Shujing Hao
Mengyao An
Chengcheng Song
Jing Li
author_facet Zijun Wu
Yuying Zhao
Shujing Hao
Mengyao An
Chengcheng Song
Jing Li
author_sort Zijun Wu
collection DOAJ
description Peroxisome proliferator-activated receptor alpha is a member of the nuclear hormone receptor superfamily and functions as a transcription factor involved in regulating cellular metabolism. Previous studies have shown that PPARα plays a key role in the onset and progression of neurodegenerative diseases. Consequently, peroxisome proliferator-activated receptor alpha agonists have garnered increasing attention as potential treatments for neurological disorders. This review aims to clarify the research progress regarding peroxisome proliferator-activated receptor alpha in nervous system diseases. Peroxisome proliferator-activated receptor alpha is present in all cell types within adult mouse and adult neural tissues. Although it is conventionally believed to be primarily localized in the nucleus, its function may be regulated by a dynamic balance between cytoplasmic and nuclear shuttling. Both endogenous and exogenous peroxisome proliferator-activated receptor alpha agonists bind to the peroxisome proliferator-activated response element to exert their biological effects. Peroxisome proliferator-activated receptor alpha plays a significant therapeutic role in neurodegenerative diseases. For instance, peroxisome proliferator-activated receptor alpha agonist gemfibrozil has been shown to reduce levels of soluble and insoluble amyloid-beta in the hippocampus of Alzheimer’s disease mouse models through the autophagy-lysosomal pathway. Additionally, peroxisome proliferator-activated receptor alpha is essential for the normal development and functional maintenance of the substantia nigra, and it can mitigate motor dysfunction in Parkinson’s disease mouse models. Furthermore, peroxisome proliferator-activated receptor alpha has been found to reduce neuroinflammation and oxidative stress in various neurological diseases. In summary, peroxisome proliferator-activated receptor alpha plays a crucial role in the onset and progression of multiple nervous system diseases, and peroxisome proliferator-activated receptor alpha agonists hold promise as new therapeutic agents for the treatment of neurodegenerative diseases, providing new options for patient care.
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spelling doaj-art-efec46adb11b4bca921230901f22aa942025-08-20T03:29:44ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53741876-79582026-04-012141468148210.4103/NRR.NRR-D-24-01371Role of peroxisome proliferator-activated receptor alpha in neurodegenerative diseases and other neurological disorders: Clinical application prospectsZijun WuYuying ZhaoShujing HaoMengyao AnChengcheng SongJing LiPeroxisome proliferator-activated receptor alpha is a member of the nuclear hormone receptor superfamily and functions as a transcription factor involved in regulating cellular metabolism. Previous studies have shown that PPARα plays a key role in the onset and progression of neurodegenerative diseases. Consequently, peroxisome proliferator-activated receptor alpha agonists have garnered increasing attention as potential treatments for neurological disorders. This review aims to clarify the research progress regarding peroxisome proliferator-activated receptor alpha in nervous system diseases. Peroxisome proliferator-activated receptor alpha is present in all cell types within adult mouse and adult neural tissues. Although it is conventionally believed to be primarily localized in the nucleus, its function may be regulated by a dynamic balance between cytoplasmic and nuclear shuttling. Both endogenous and exogenous peroxisome proliferator-activated receptor alpha agonists bind to the peroxisome proliferator-activated response element to exert their biological effects. Peroxisome proliferator-activated receptor alpha plays a significant therapeutic role in neurodegenerative diseases. For instance, peroxisome proliferator-activated receptor alpha agonist gemfibrozil has been shown to reduce levels of soluble and insoluble amyloid-beta in the hippocampus of Alzheimer’s disease mouse models through the autophagy-lysosomal pathway. Additionally, peroxisome proliferator-activated receptor alpha is essential for the normal development and functional maintenance of the substantia nigra, and it can mitigate motor dysfunction in Parkinson’s disease mouse models. Furthermore, peroxisome proliferator-activated receptor alpha has been found to reduce neuroinflammation and oxidative stress in various neurological diseases. In summary, peroxisome proliferator-activated receptor alpha plays a crucial role in the onset and progression of multiple nervous system diseases, and peroxisome proliferator-activated receptor alpha agonists hold promise as new therapeutic agents for the treatment of neurodegenerative diseases, providing new options for patient care.https://journals.lww.com/10.4103/NRR.NRR-D-24-01371agonistsalzheimer’s diseasegut microbiotamultiple sclerosisnervous system diseaseneurodegenerationneurodegenerative diseaseneuroinflammationparkinson’s diseaseperoxisome proliferator-activated receptor alpha
spellingShingle Zijun Wu
Yuying Zhao
Shujing Hao
Mengyao An
Chengcheng Song
Jing Li
Role of peroxisome proliferator-activated receptor alpha in neurodegenerative diseases and other neurological disorders: Clinical application prospects
Neural Regeneration Research
agonists
alzheimer’s disease
gut microbiota
multiple sclerosis
nervous system disease
neurodegeneration
neurodegenerative disease
neuroinflammation
parkinson’s disease
peroxisome proliferator-activated receptor alpha
title Role of peroxisome proliferator-activated receptor alpha in neurodegenerative diseases and other neurological disorders: Clinical application prospects
title_full Role of peroxisome proliferator-activated receptor alpha in neurodegenerative diseases and other neurological disorders: Clinical application prospects
title_fullStr Role of peroxisome proliferator-activated receptor alpha in neurodegenerative diseases and other neurological disorders: Clinical application prospects
title_full_unstemmed Role of peroxisome proliferator-activated receptor alpha in neurodegenerative diseases and other neurological disorders: Clinical application prospects
title_short Role of peroxisome proliferator-activated receptor alpha in neurodegenerative diseases and other neurological disorders: Clinical application prospects
title_sort role of peroxisome proliferator activated receptor alpha in neurodegenerative diseases and other neurological disorders clinical application prospects
topic agonists
alzheimer’s disease
gut microbiota
multiple sclerosis
nervous system disease
neurodegeneration
neurodegenerative disease
neuroinflammation
parkinson’s disease
peroxisome proliferator-activated receptor alpha
url https://journals.lww.com/10.4103/NRR.NRR-D-24-01371
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