Circadian rhythm as a therapeutic target

Every organism has an intrinsic biological rhythm that orchestrates biological processes in adjusting to daily environmental changes. Circadian rhythms are maintained by networks of molecular clocks throughout the core and peripheral tissues, including immune cells, blood vessels, and perivascular adipose tissues. Recent findings have suggested strong correlations between the circadian clock and cardiovascular diseases. Desynchronization between the circadian rhythm and body metabolism contributes to the development of cardiovascular diseases including arteriosclerosis and thrombosis. Circadian rhythms are involved in controlling inflammatory processes and metabolisms, which can influence the pathology of arteriosclerosis and thrombosis. Circadian clock genes are critical in maintaining the robust relationship between diurnal variation and the cardiovascular system. The circadian machinery in the vascular system may be a novel therapeutic target for the prevention and treatment of cardiovascular diseases. The research on circadian rhythms in cardiovascular diseases is still progressing. In this review, we briefly summarize recent studies on circadian rhythms and cardiovascular homeostasis, focusing on the circadian control of inflammatory processes and metabolisms. Based on the recent findings, we discuss the potential target molecules for future therapeutic strategies against cardiovascular diseases by targeting the circadian clock.

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PPARα is a potential therapeutic target of drugs to treat circadian rhythm sleep disorders

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2007.04.002 ◽

2007 ◽

Vol 357 (3) ◽

pp. 679-682 ◽

Cited By ~ 47

Author(s):

Hidenori Shirai ◽

Katsutaka Oishi ◽

Takashi Kudo ◽

Shigenobu Shibata ◽

Norio Ishida

Keyword(s):

Circadian Rhythm ◽

Sleep Disorders ◽

Therapeutic Target ◽

Potential Therapeutic Target ◽

Circadian Rhythm Sleep Disorders

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The Neuroprotective Effects of Melatonin: Possible Role in the Pathophysiology of Neuropsychiatric Disease

Brain Sciences ◽

10.3390/brainsci9100285 ◽

2019 ◽

Vol 9 (10) ◽

pp. 285 ◽

Cited By ~ 5

Author(s):

Jung Goo Lee ◽

Young Sup Woo ◽

Sung Woo Park ◽

Dae-Hyun Seog ◽

Mi Kyoung Seo ◽

...

Keyword(s):

Antioxidant Activity ◽

Circadian Rhythm ◽

Molecular Biology ◽

Pineal Gland ◽

Mechanism Of Action ◽

Therapeutic Target ◽

New Drugs ◽

Sleep Cycle ◽

Neuroprotective Effects ◽

Neuropsychiatric Disease

Melatonin is a hormone that is secreted by the pineal gland. To date, melatonin is known to regulate the sleep cycle by controlling the circadian rhythm. However, recent advances in neuroscience and molecular biology have led to the discovery of new actions and effects of melatonin. In recent studies, melatonin was shown to have antioxidant activity and, possibly, to affect the development of Alzheimer’s disease (AD). In addition, melatonin has neuroprotective effects and affects neuroplasticity, thus indicating potential antidepressant properties. In the present review, the new functions of melatonin are summarized and a therapeutic target for the development of new drugs based on the mechanism of action of melatonin is proposed.

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Memapsin 2, a drug target for Alzheimer's disease

Biochemical Society Symposium ◽

10.1042/bss0700213 ◽

2003 ◽

Vol 70 ◽

pp. 213-220 ◽

Cited By ~ 1

Author(s):

Gerald Koelsch ◽

Robert T. Turner ◽

Lin Hong ◽

Arun K. Ghosh ◽

Jordan Tang

Keyword(s):

Crystal Structure ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Transition State ◽

Amyloid Precursor Protein ◽

Therapeutic Target ◽

Drug Target ◽

Aspartic Protease ◽

Precursor Protein ◽

Memapsin 2

Mempasin 2, a ϐ-secretase, is the membrane-anchored aspartic protease that initiates the cleavage of amyloid precursor protein leading to the production of ϐ-amyloid and the onset of Alzheimer's disease. Thus memapsin 2 is a major therapeutic target for the development of inhibitor drugs for the disease. Many biochemical tools, such as the specificity and crystal structure, have been established and have led to the design of potent and relatively small transition-state inhibitors. Although developing a clinically viable mempasin 2 inhibitor remains challenging, progress to date renders hope that memapsin 2 inhibitors may ultimately be useful for therapeutic reduction of ϐ-amyloid.

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