Melatonin derivative 6a as a PARP-1 inhibitor for the treatment of Parkinson’s disease

Autor: Qing-Wei Ma, Rui-Ting Han, Zi-Jie Wu, Jun-Jie Zhou, Meng-Ting Chen, Xiang-Zhi Zhang, Wen-Zhe Ma, Na Feng
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Frontiers in Pharmacology, Vol 15 (2024)
Druh dokumentu: article
ISSN: 1663-9812
DOI: 10.3389/fphar.2024.1363212
Popis: 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 α-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.
Databáze: Directory of Open Access Journals