Matches in SemOpenAlex for { <https://semopenalex.org/work/W4200215747> ?p ?o ?g. }
- W4200215747 abstract "Abstract 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 ( H eat S hock P rotein) 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. Summary Statement This study shows, for the first time, a neuroprotective role of chaperone HSP40 in overcoming circadian dysfunction associated with Huntington’s Disease in a Drosophila model" @default.
- W4200215747 created "2021-12-31" @default.
- W4200215747 creator A5004753731 @default.
- W4200215747 creator A5035690583 @default.
- W4200215747 creator A5076453215 @default.
- W4200215747 date "2021-12-28" @default.
- W4200215747 modified "2023-09-26" @default.
- W4200215747 title "HSP40 overexpression in pacemaker neurons protects against circadian dysfunction in a <i>Drosophila</i> model of Huntington’s Disease" @default.
- W4200215747 cites W1523616760 @default.
- W4200215747 cites W1566316384 @default.
- W4200215747 cites W1567631042 @default.
- W4200215747 cites W1588034954 @default.
- W4200215747 cites W1643390591 @default.
- W4200215747 cites W1970108896 @default.
- W4200215747 cites W1972121275 @default.
- W4200215747 cites W1973830626 @default.
- W4200215747 cites W1974456128 @default.
- W4200215747 cites W1980839410 @default.
- W4200215747 cites W1982623268 @default.
- W4200215747 cites W1986846248 @default.
- W4200215747 cites W1987074547 @default.
- W4200215747 cites W1988146888 @default.
- W4200215747 cites W1992921611 @default.
- W4200215747 cites W1995008214 @default.
- W4200215747 cites W1995866702 @default.
- W4200215747 cites W1996511867 @default.
- W4200215747 cites W1996972628 @default.
- W4200215747 cites W2000446177 @default.
- W4200215747 cites W2001299798 @default.
- W4200215747 cites W2002431899 @default.
- W4200215747 cites W2003416174 @default.
- W4200215747 cites W2004070915 @default.
- W4200215747 cites W2006872992 @default.
- W4200215747 cites W2008410014 @default.
- W4200215747 cites W2008586929 @default.
- W4200215747 cites W2009278076 @default.
- W4200215747 cites W2010795572 @default.
- W4200215747 cites W2014451752 @default.
- W4200215747 cites W2019477206 @default.
- W4200215747 cites W2031473689 @default.
- W4200215747 cites W2035531816 @default.
- W4200215747 cites W2038911675 @default.
- W4200215747 cites W2039820061 @default.
- W4200215747 cites W2043772894 @default.
- W4200215747 cites W2055643502 @default.
- W4200215747 cites W2058887020 @default.
- W4200215747 cites W2058947907 @default.
- W4200215747 cites W2060570462 @default.
- W4200215747 cites W2060750433 @default.
- W4200215747 cites W2063389767 @default.
- W4200215747 cites W2065861852 @default.
- W4200215747 cites W2067297186 @default.
- W4200215747 cites W2069102506 @default.
- W4200215747 cites W2071250433 @default.
- W4200215747 cites W2072925339 @default.
- W4200215747 cites W2073687064 @default.
- W4200215747 cites W2074591242 @default.
- W4200215747 cites W2076581533 @default.
- W4200215747 cites W2077983593 @default.
- W4200215747 cites W2078010704 @default.
- W4200215747 cites W2086111504 @default.
- W4200215747 cites W2089503385 @default.
- W4200215747 cites W2092340914 @default.
- W4200215747 cites W2092986760 @default.
- W4200215747 cites W2099328856 @default.
- W4200215747 cites W2099540110 @default.
- W4200215747 cites W2102007653 @default.
- W4200215747 cites W2106786078 @default.
- W4200215747 cites W2107007950 @default.
- W4200215747 cites W2107764105 @default.
- W4200215747 cites W2108180838 @default.
- W4200215747 cites W2110169380 @default.
- W4200215747 cites W2112360818 @default.
- W4200215747 cites W2113526393 @default.
- W4200215747 cites W2120071939 @default.
- W4200215747 cites W2122674036 @default.
- W4200215747 cites W2123294439 @default.
- W4200215747 cites W2126357344 @default.
- W4200215747 cites W2128067123 @default.
- W4200215747 cites W2131631598 @default.
- W4200215747 cites W2132513906 @default.
- W4200215747 cites W2132616469 @default.
- W4200215747 cites W2134022293 @default.
- W4200215747 cites W2135880722 @default.
- W4200215747 cites W2136201006 @default.
- W4200215747 cites W2138070282 @default.
- W4200215747 cites W2140197221 @default.
- W4200215747 cites W2141100785 @default.
- W4200215747 cites W2145631524 @default.
- W4200215747 cites W2147340177 @default.
- W4200215747 cites W2148505202 @default.
- W4200215747 cites W2149761960 @default.
- W4200215747 cites W2151030753 @default.
- W4200215747 cites W2152217159 @default.
- W4200215747 cites W2156079900 @default.
- W4200215747 cites W2157860878 @default.
- W4200215747 cites W2162871402 @default.
- W4200215747 cites W2164890075 @default.
- W4200215747 cites W2167636534 @default.
- W4200215747 cites W2168037738 @default.