dc.contributor.author |
Prakash, Pavitra |
|
dc.contributor.author |
Kumar Pradhan, Arpit |
|
dc.contributor.author |
Sheeba, Vasu |
|
dc.date.accessioned |
2022-06-02T08:35:30Z |
|
dc.date.available |
2022-06-02T08:35:30Z |
|
dc.date.issued |
2022-05-30 |
|
dc.identifier.citation |
Pavitra Prakash, Arpit Kumar Pradhan, Vasu Sheeba; HSP40 overexpression in pacemaker neurons protects against circadian dysfunction in a Drosophila model of Huntington's Disease. Dis Model Mech 2022; dmm.049447. doi: https://doi.org/10.1242/dmm.049447 |
en_US |
dc.identifier.other |
https://doi.org/10.1242/dmm.049447 |
|
dc.identifier.uri |
https://libjncir.jncasr.ac.in/xmlui/handle/123456789/3251 |
|
dc.description |
This study shows, for the first time, a neuroprotective role of chaperone HSP40 in suppressing circadian dysfunction associated with Huntington’s Disease in a Drosophila model. |
en_US |
dc.description.abstract |
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. |
en_US |
dc.description.sponsorship |
Department of Science and Technology (SR/S2/RJN-42/2008), Council of Science and Industrial Research (09/733(0117)/2009-EMR-I), INSPIRE Fellowship. |
en_US |
dc.language.iso |
en |
en_US |
dc.publisher |
Disease Models and Mechanisms |
en_US |
dc.subject |
Circadian |
en_US |
dc.subject |
Heat Shock Protein (HSP) |
en_US |
dc.subject |
HSP40 |
en_US |
dc.subject |
Huntingtin |
en_US |
dc.subject |
Huntington’s Disease |
en_US |
dc.subject |
Neurodegeneration |
en_US |
dc.subject |
Drosophila |
en_US |
dc.subject |
LNv |
en_US |
dc.title |
HSP40 overexpression in pacemaker neurons protects against circadian dysfunction in a Drosophila model of Huntington's Disease |
en_US |
dc.type |
Article |
en_US |