1. Melatonin derivative 6a as a PARP-1 inhibitor for the treatment of Parkinson's disease.
- Author
-
Qing-Wei Ma, Rui-Ting Han, Zi-Jie Wu, Jun-Jie Zhou, Meng-Ting Chen, Xiang-Zhi Zhang, Wen-Zhe Ma, and Na Feng
- Subjects
HEAT shock proteins ,PARKINSON'S disease ,POLY(ADP-ribose) polymerase ,HEAT shock factors ,DOPA ,MELATONIN ,CAENORHABDITIS elegans - Abstract
Both continuous oxidative stress and poly (ADP-ribose) polymerase 1 (PARP-1) activation occur in neurodegenerative diseases such as Parkinson's disease. PARP-1 inhibition can reverse mitochondrial damage and has a neuroprotective effect. In a previous study, we synthesized melatonin derivative 6a (MD6a) and reported that it has excellent antioxidant activity and significantly reduces a-synuclein aggregation in Caenorhabditis elegans; however, the underlying mechanism is largely unknown. In the present study, we revealed that MD6a is a potential PARP-1 inhibitor, leading to mammalian targe of rapamycin/heat shock factor 1 signaling downregulation and reducing heat shock protein 4 and 6 expression, thus helping to maintain protein homeostasis and improve mitochondrial function. Together, these findings suggest that MD6a might be a viable candidate for the prevention and treatment of Parkinson's disease. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF