Metabolic Basis of Circadian Dysfunction in Parkinson’s Disease

SIMPLE SUMMARY: Parkinson’s disease (PD) is the second most common neurodegenerative disorder. Although genetic predisposition plays an important role, circadian dysfunction caused by chronic sleep disorders in response to the industrialization of modern society has increased the prevalence of PD. This review highlights the intricate interplay between circadian rhythm, cellular metabolism, and PD pathogenesis. Understanding the metabolic underpinnings of circadian dysfunction in PD could lead to identifying novel biomarkers for early diagnosis of PD and developing targeted therapeutic strategies to better manage and treat this complex neurodegenerative disorder. ABSTRACT: Parkinson’s disease (PD) is one of the most common neurodegenerative disorders. The management of PD is a challenging aspect for general physicians and neurologists. It is characterized by the progressive loss of dopaminergic neurons. Impaired α-synuclein secretion and dopamine release may cause mitochondrial dysfunction and perturb energy metabolism, subsequently altering the activity and survival of dopaminergic neurons, thus perpetuating the neurodegenerative process in PD. While the etiology of PD remains multifactorial, emerging research indicates a crucial role of circadian dysfunction in its pathogenesis. Researchers have revealed that circadian dysfunction and sleep disorders are common among PD subjects and disruption of circadian rhythms can increase the risk of PD. Hence, understanding the findings of circadian biology from translational research in PD is important for reducing the risk of neurodegeneration and for improving the quality of life. In this review, we discuss the intricate relationship between circadian dysfunction in cellular metabolism and PD by summarizing the evidence from animal models and human studies. Understanding the metabolic basis of circadian dysfunction in PD may shed light on novel therapeutic approaches to restore circadian rhythm, preserve dopaminergic function, and ameliorate disease progression. Further investigation into the complex interplay between circadian rhythm and PD pathogenesis is essential for the development of targeted therapies and interventions to alleviate the burden of this debilitating neurodegenerative disorder.