Mutant huntingtin disturbs circadian clock gene expression and sleep patterns in Drosophila

Faragó, Anikó; Zsindely, Nóra; Bodai, László

doi:10.1038/s41598-019-43612-w

Cited by 21 publications

(19 citation statements)

References 33 publications

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“…However, a Drosophila model of HD demonstrated conflicting evidence. Mutant flies had abnormally prolonged expression of PER and TIMELESS (another component of the Drosophila negative arm) and hallmark circadian activity disturbances ( Farago et al, 2019 ) indicating a disrupted TTFL In mammals, PER1 and PER2 are also important players in photic entrainment., and both are deregulated in symptomatic HD mice with retinal degeneration ( Morton et al, 2005 ). As a result, mice have reduced light sensitivity.…”

Section: Huntington’s Diseasementioning

confidence: 99%

The Molecular Clock and Neurodegenerative Disease: A Stressful Time

Carter

Justin

Gulick

et al. 2021

Front. Mol. Biosci.

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Circadian rhythm dysfunction occurs in both common and rare neurodegenerative diseases. This dysfunction manifests as sleep cycle mistiming, alterations in body temperature rhythms, and an increase in symptomatology during the early evening hours known as Sundown Syndrome. Disruption of circadian rhythm homeostasis has also been implicated in the etiology of neurodegenerative disease. Indeed, individuals exposed to a shifting schedule of sleep and activity, such as health care workers, are at a higher risk. Thus, a bidirectional relationship exists between the circadian system and neurodegeneration. At the heart of this crosstalk is the molecular circadian clock, which functions to regulate circadian rhythm homeostasis. Over the past decade, this connection has become a focal point of investigation as the molecular clock offers an attractive target to combat both neurodegenerative disease pathogenesis and circadian rhythm dysfunction, and a pivotal role for neuroinflammation and stress has been established. This review summarizes the contributions of molecular clock dysfunction to neurodegenerative disease etiology, as well as the mechanisms by which neurodegenerative diseases affect the molecular clock.

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Section: Huntington’s Diseasementioning

confidence: 99%

The Molecular Clock and Neurodegenerative Disease: A Stressful Time

Carter

Justin

Gulick

et al. 2021

Front. Mol. Biosci.

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“…Circadian gene expression is impaired in HD model flies [187]. Delayed acrophase of per and tim in HD flies correlates with delayed nighttime sleep.…”

Section: Huntington's Diseasementioning

confidence: 98%

MicroRNA: A Key Player for the Interplay of Circadian Rhythm Abnormalities, Sleep Disorders and Neurodegenerative Diseases

et al. 2020

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Circadian rhythms are endogenous 24-h oscillators that regulate the sleep/wake cycles and the timing of biological systems to optimize physiology and behavior for the environmental day/night cycles. The systems are basically generated by transcription–translation feedback loops combined with post-transcriptional and post-translational modification. Recently, evidence is emerging that additional non-coding RNA-based mechanisms are also required to maintain proper clock function. MicroRNA is an especially important factor that plays critical roles in regulating circadian rhythm as well as many other physiological functions. Circadian misalignment not only disturbs the sleep/wake cycle and rhythmic physiological activity but also contributes to the development of various diseases, such as sleep disorders and neurodegenerative diseases. The patient with neurodegenerative diseases often experiences profound disruptions in their circadian rhythms and/or sleep/wake cycles. In addition, a growing body of recent evidence implicates sleep disorders as an early symptom of neurodegenerative diseases, and also suggests that abnormalities in the circadian system lead to the onset and expression of neurodegenerative diseases. The genetic mutations which cause the pathogenesis of familial neurodegenerative diseases have been well studied; however, with the exception of Huntington’s disease, the majority of neurodegenerative diseases are sporadic. Interestingly, the dysfunction of microRNA is increasingly recognized as a cause of sporadic neurodegenerative diseases through the deregulated genes related to the pathogenesis of neurodegenerative disease, some of which are the causative genes of familial neurodegenerative diseases. Here we review the interplay of circadian rhythm disruption, sleep disorders and neurodegenerative disease, and its relation to microRNA, a key regulator of cellular processes.

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“…In a DST shift effect analysis, one should keep in mind that there are two distinct phenomena in play: (1) the natural variation of day length, the amount of light over the year, and the daily sunlight intensity cycle affects the human circadian clock, behavior, and numerous diseases [29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45], and; (2) the disruption of individuals' daily schedule due to the DST shift. Our analyses were designed to target the effects associated with the latter, adjusting for the former with negative controls.…”

Section: Plos Computational Biologymentioning

confidence: 99%

Measurable health effects associated with the daylight saving time shift

et al. 2020

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The transition to daylight saving time (DST) is beneficial for energy conservation but at the same time it has been reported to increase the risk of cerebrovascular and cardiovascular problems. Here, we evaluate the effect of the DST shift on a whole spectrum of diseasesan analysis we hope will be helpful in weighing the risks and benefits of DST shifts. Our study relied on a population-based, cross-sectional analysis of the IBM Watson Health Mar-ketScan insurance claim dataset, which incorporates over 150 million unique patients in the US, and the Swedish national inpatient register, which incorporates more than nine million unique Swedes. For hundreds of sex-and age-specific diseases, we assessed effects of the DST shifts forward and backward by one hour in spring and autumn by comparing the observed and expected diagnosis rates after DST shift exposure. We found four prominent, elevated risk clusters, including cardiovascular diseases (such as heart attacks), injuries, mental and behavioral disorders, and immune-related diseases such as noninfective enteritis and colitis to be significantly associated with DST shifts in the United States and Sweden. While the majority of disease risk elevations are modest (a few percent), a considerable number of diseases exhibit an approximately ten percent relative risk increase. We estimate that each spring DST shift is associated with negative health effects-with 150,000 incidences in the US, and 880,000 globally. We also identify for the first time a collection of diseases with relative risks that appear to decrease immediately after the spring DST shift, enriched with infections and immune system-related maladies. These diseases' decreasing relative risks might be driven by the documented boosting effect of a short-term stress (such as that experienced around the spring DST shift) on the immune system.

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Mutant huntingtin disturbs circadian clock gene expression and sleep patterns in Drosophila

Cited by 21 publications

References 33 publications

The Molecular Clock and Neurodegenerative Disease: A Stressful Time

The Molecular Clock and Neurodegenerative Disease: A Stressful Time

MicroRNA: A Key Player for the Interplay of Circadian Rhythm Abnormalities, Sleep Disorders and Neurodegenerative Diseases

Measurable health effects associated with the daylight saving time shift

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