Abstract

Despite varied etiologies and symptoms, several neurodegenerative diseases—specifically, Alzheimer’s (AD), Parkinson’s (PD), and Huntington’s diseases (HDs)—share the common feature of abnormal circadian rhythms, such as those in behavior (e.g., disrupted sleep/wake cycles), physiological processes (e.g., diminished hormone release) and biochemical activities (e.g., antioxidant production). Circadian disturbances are among the earliest symptoms of these diseases, and the molecular mechanisms of the circadian system are suspected to play a pivotal, and possibly causal, role in their natural histories. Here, we review the common circadian abnormalities observed in ADs, PDs and HDs, and summarize the evidence that the molecular circadian clockwork directly influences the course of these disease states. On the basis of this research, we explore several circadian-oriented interventions proposed as treatments for these neurological disorders.

Highlights

  • Despite varied etiologies and symptoms, several neurodegenerative diseases—Alzheimer’s (AD), Parkinson’s (PD), and Huntington’s diseases (HDs)—share the common feature of abnormal circadian rhythms, such as those in behavior, physiological processes and biochemical activities

  • We review the common circadian abnormalities observed in Alzheimer’s disease (AD), Parkinson’s disease (PD) and HDs, and summarize the evidence that the molecular circadian clockwork directly influences the course of these disease states

  • The lack of evidence that timed light exposure and melatonin administration improve the non-circadian symptoms of AD, PD and HD would seem to undermine the idea that the circadian system contributes to the etiology of these neurodegenerative diseases

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Summary

Neurodegeneration and the Circadian Clock

Reviewed by: Lakshmi Rajagopal, Northwestern University, United States Umesh Gangishetti, Emory University, United States. Despite varied etiologies and symptoms, several neurodegenerative diseases—Alzheimer’s (AD), Parkinson’s (PD), and Huntington’s diseases (HDs)—share the common feature of abnormal circadian rhythms, such as those in behavior (e.g., disrupted sleep/wake cycles), physiological processes (e.g., diminished hormone release) and biochemical activities (e.g., antioxidant production). Circadian disturbances are among the earliest symptoms of these diseases, and the molecular mechanisms of the circadian system are suspected to play a pivotal, and possibly causal, role in their natural histories. We review the common circadian abnormalities observed in ADs, PDs and HDs, and summarize the evidence that the molecular circadian clockwork directly influences the course of these disease states. On the basis of this research, we explore several circadian-oriented interventions proposed as treatments for these neurological disorders

CIRCADIAN RHYTHMS AND NEURODEGENERATIVE DISEASES
Circadian Rhythms and Cellular Clocks
Melatonin and Cortisol Rhythms
Core Body Temperature Rhythm
Mood and Behavior Rhythm
NEURODEGENERATIVE DISEASES AND CLOCK GENE EXPRESSION
DOES A FAULTY CIRCADIAN CLOCK CAUSE NEURODEGENERATIVE DISEASE?
CONCLUSIONS
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