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HSP40 overexpression in pacemaker neurons protects against circadian dysfunction in a Drosophila model of Huntington's Disease

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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


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