Molecular mechanisms of exercise-induced neuroprotection against Parkinson's disease

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disease that affects movement and cognitive function, resulting from the loss of the neurotransmitter dopamine due to the death of dopaminergic neurons. It affects nearly one million people in the United States and 8.5 million worldwide. While there are some pharmacological and surgical options available, they only provide symptomatic relief, as there is currently no cure for PD. In contrast, exercise training, a non-pharmacological intervention, has emerged as a powerful strategy to enhance the psychological, cognitive, and physiological (motor) impairments associated with PD. Given that the beneficial effects of exercise differ based on the intensity and type of training, gaining a thorough understanding of the molecular mechanisms underlying exercise-induced protection is crucial for developing innovative therapies that improve the quality of life for PD patients around the globe. This review discusses PD pathogenesis and pathophysiology and provides recent clinical evidence of neuroprotective benefits from various exercise modalities and intensity. Furthermore, the molecular mechanisms of exercise in PD pathogenesis (e.g., modulations on neurotrophic factors, oxidative stress, mitochondria dysfunction, endoplasmic reticulum stress, and autophagy) will be emphasized.

Keywords

Parkinson's disease / Exercise / Mitochondria / Autophagy / Oxidative stress

CRediT authorship contribution statement

Youngil Lee: Writing - review & editing, Writing - original draft, Visualization, Supervision, Methodology, Conceptualization. Beomsoo Ju: Writing - review & editing, Visualization, Data curation, Conceptualization. Yohan Cheon: Writing - review & editing, Visualization, Data curation. Namita Mishra: Writing - review & editing, Writing - original draft, Conceptualization. Emma Fletcher: Writing - review & editing. Panagiotis Koutakis: Writing - review & editing. Gulnaz T. Javan: Writing - review & editing. Young C. Jang: Writing - review & editing.

Funding statement

This work was supported by an AIMS fellowship grant from the University of West Florida (04523: YL) and partially by the National Institutes of Health grant under Award Number R16-GM149358 and the National Science Foundation grant DUE 2344997.

Declaration of competing interest

The authors declare they have no financial interests/personal relationships that could have appeared to influence the work reported in this paper.

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