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Current Alzheimer Research

Current Alzheimer Research

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ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

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Review Article

Mapping the Connection Between Circadian Rhythms, Metabolism, and Neurodegeneration: Exploring Therapeutic Strategies

Author(s): Rakesh Bhaskar*, Kannan Badri Narayanan, Krishna Kumar Singh and Sung Soo Han*

Volume 22, Issue 9, 2025

Published on: 16 July, 2025

Page: [678 - 697] Pages: 20

DOI: 10.2174/0115672050381989250626071304

Price: $65

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Abstract

Circadian rhythms are crucial for essential physiological functions such as metabolism, sleep-wake cycles, hormone balance, and cognitive abilities, which are regulated by the central Suprachiasmatic Nucleus (SCN) and peripheral clocks. Disruptions to circadian rhythms, which may be caused by aging, lifestyle factors, and environmental influences, are linked to metabolic disorders and Neurodegenerative Diseases (NDs). This review examines the reciprocal relationship between circadian control and metabolism, highlighting the molecular processes that maintain circadian rhythms and how these processes change with age. Aging diminishes SCN efficiency and disrupts peripheral clock alignment, leading to impaired physiological functions, increased oxidative stress, and neuroinflammation, all of which contribute to the progression of NDs such as Alzheimer’s (AD), Parkinson's disease (PD), Huntington's disease (HD), etc. Emerging therapeutic strategies aim to restore circadian function through interventions, including bright light therapy, melatonin supplementation, and pharmacological agents targeting clock gene regulators and neuropeptides. Furthermore, lifestyle modifications, such as Structured Physical Activity (SPA) and Time-Restricted Feeding (TRF), can enhance circadian health by synchronizing metabolic and hormonal rhythms. Future directions include chrono-pharmacology, gene editing, and Artificial Intelligence (AI)-driven personalized medicine, all of which emphasize the development of tailored circadian therapies. Advancing circadian research holds the potential to facilitate better health outcomes and improve quality of life, while also addressing the growing concerns of the aging population and NDs.

Keywords: Circadian rhythm, aging, bright light therapy, neurodegenerative disorder, chrono-pharmacology, melatonin.

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