Circadian Rhythms and Proteostasis in Aging

Desvergne, Audrey; Friguet, Bertrand

doi:10.1007/978-3-319-64543-8_8

Cited by 4 publications

(4 citation statements)

References 135 publications

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“…There is ample evidence for clock-controlled regulation of proteostasis components, including chaperones ( Desvergne and Friguet, 2017 ; Ryzhikov et al, 2019 ; Wang et al, 2020 ), with both Hsp40 and Hsp70 isoforms showing rhythmic gene expression across taxa ( Li et al, 2017 ). In the Drosophila LNv, mRNA transcripts of the Hsp40 isoforms, DnaJ-1 and the DnaJ-H are present, and, in the lLNv, DnaJ-H gene expression is cyclic ( Kula-Eversole et al, 2010 ; Ma et al, 2021 ), while Hsp70 transcripts cycle in the LNv ( Abruzzi et al, 2017 ; Ma et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Hsp40 overexpression in pacemaker neurons delays circadian dysfunction in a Drosophila model of Huntington's disease

Prakash

Pradhan

Sheeba

2022

Disease Models &Amp; Mechanisms

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Circadian disturbances are early features of neurodegenerative diseases, including Huntington's Disease (HD). Emerging evidence suggests that circadian decline feeds into neurodegenerative symptoms, exacerbating them. Therefore, we asked whether known neurotoxic modifiers can suppress circadian dysfunction. We performed a screen of neurotoxicity-modifier genes to suppress circadian behavioural arrhythmicity in a Drosophila circadian HD model. The molecular chaperones HSP40 and HSP70 (Heat Shock Protein) emerged as significant suppressors in the circadian context, with HSP40 being the more potent mitigator. Upon HSP40 overexpression in the Drosophila circadian ventrolateral neurons (LNv), the behavioural rescue was associated with neuronal rescue of loss of circadian proteins from small LNv soma. Specifically, there was a restoration of the molecular clock protein Period and its oscillations in young flies and a long-lasting rescue of the output neuropeptide Pigment Dispersing Factor. Significantly, there was a reduction in the expanded Huntingtin inclusion load, concomitant with the appearance of a spot-like Huntingtin form. Thus, we provide evidence implicating the neuroprotective chaperone HSP40 in circadian rehabilitation. The involvement of molecular chaperones in circadian maintenance has broader therapeutic implications for neurodegenerative diseases.

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Section: Discussionmentioning

confidence: 99%

Hsp40 overexpression in pacemaker neurons delays circadian dysfunction in a Drosophila model of Huntington's disease

Prakash

Pradhan

Sheeba

2022

Disease Models &Amp; Mechanisms

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“…This pathway is responsible for removing toxins and recycling wastes from cells and tissues. The ubiquitin proteasome pathway regulates and is reciprocally regulated by the circadian timing system [28]. The ubiquitin proteasomal pathway is a key regulator of the degradation of the core clock components PER and CRY, which in turn relieves their inhibition of BMAL1:CLOCK activity [29].…”

Section: Discussionmentioning

confidence: 99%

“…Progressive aging is marked by the buildup of damaged proteins that result partially from oxidative damage. Thus, the proteome signature of PS-treated cattle may reflect the effects of circadian clock disruption [28].…”

Section: Discussionmentioning

confidence: 99%

Impact of Exposure to Chronic Light–Dark Phase Shifting Circadian Rhythm Disruption on Muscle Proteome in Periparturient Dairy Cows

2021

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Muscle tissue serves as a key nutrient reservoir that dairy cows utilize to meet energy and amino acid requirements for fetal growth and milk production. Circadian clocks act as homeostatic regulators so that organisms can anticipate regular environmental changes. The objective of this study was to use liquid chromatography tandem mass spectrometry (LC-MS/MS) to determine how chronic circadian disruption in late gestation affected the muscle tissue proteome. At five weeks before expected calving (BEC), multiparous Holstein cows were assigned to either a control (CON, n = 8) or a 6 h forward phase shift (PS, n = 8) of the light–dark cycle every 3 days. At calving, all animals were exposed to CON light–dark cycles. Muscle biopsies were collected from longissimus dorsi muscles at 21 days BEC and at 21 days postpartum (PP). At p < 0.1, 116 and 121 proteins were differentially abundant between PS and CON at 21 days BEC and 21 days PP, respectively. These proteins regulate beta oxidation and glycolysis. Between pregnancy and lactation, 134 and 145 proteins were differentially abundant in CON and PS cows, respectively (p < 0.1). At both timepoints, PS cows exhibited an oxidative stress signature. Thus, dairy cattle management strategies that minimize circadian disruptions may ensure optimal health and production performance.

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“…There is ample evidence for clock-control regulation of proteostasis components, including chaperones (Desvergne and Friguet, 2017;Ryzhikov et al, 2019;Wang et al, 2020), with both HSP40 and HSP70 isoforms, showing rhythmic gene expression across taxa (Li et al, 2017).…”

Section: Hsps Circadian Health and Neurodegenerative Diseasesmentioning

confidence: 99%

HSP40 overexpression in pacemaker neurons protects against circadian dysfunction in aDrosophilamodel of Huntington’s Disease

Prakash

Pradhan

Sheeba

2021

Preprint

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Circadian disturbances are early features of neurodegenerative diseases, including Huntington's Disease (HD), affecting the quality of life of patients and caregivers. Emerging evidence suggests that circadian decline feeds-forward to neurodegenerative symptoms, exacerbating them, highlighting a need for restoring circadian health. Therefore, we asked whether any of the known neurotoxic modifiers can suppress circadian dysfunction. We performed a screen of neurotoxicity-modifier genes to suppress circadian behavioural arrhythmicity in a Drosophila circadian HD model. Notably, the molecular chaperones HSP40 and HSP70 (Heat Shock Protein) emerged as significant suppressors in the circadian context, with HSP40 being the more potent mitigator of HD-induced deficits. Upon HSP40 overexpression in the Drosophila circadian ventrolateral neurons (LNv), the behavioural rhythm rescue was associated with neuronal rescue of loss in circadian proteins from small LNv soma. Specifically, there was a restoration of the molecular clock protein Period and its oscillations in young flies and a long-lasting rescue of the output neuropeptide Pigment Dispersing Factor. Significantly, there was a reduction in the expanded Huntingtin inclusion load, concomitant with the appearance of a spot-like Huntingtin form. Thus, we provide evidence for the first time that implicates the neuroprotective chaperone HSP40 in circadian rehabilitation. Given the importance of proteostasis and circadian health in neurodegenerative diseases, the involvement of molecular chaperones in circadian maintenance has broader therapeutic implications.

show abstract

Circadian Rhythms and Proteostasis in Aging

Cited by 4 publications

References 135 publications

Hsp40 overexpression in pacemaker neurons delays circadian dysfunction in a Drosophila model of Huntington's disease

Hsp40 overexpression in pacemaker neurons delays circadian dysfunction in a Drosophila model of Huntington's disease

Impact of Exposure to Chronic Light–Dark Phase Shifting Circadian Rhythm Disruption on Muscle Proteome in Periparturient Dairy Cows

HSP40 overexpression in pacemaker neurons protects against circadian dysfunction in aDrosophilamodel of Huntington’s Disease

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