Pharmacological PINK1 activation ameliorates Pathology in Parkinson's Disease models.

Randall Marcelo ChinRishi RakhitDara DitsworthChengzhong WangJohan BartholomeusSong LiuAkash ModyAlex LaishuAndrea N EastesChao TaiRoy Y KimJessica LiSteven HansberrySaurabh KhasnavisVictoria RafalskiDonald HerendeenVirginia GardaJennie PhungDaniel de RouletAlban Ordureau J Wade Harper Shawn Johnstone Jan Stöhr Nicholas T Hertz

Published in: bioRxiv : the preprint server for biology (2023)

Discovery of a plasma Parkinson's Disease biomarker candidate, pS65-Ubiquitin (pUb)Plasma pUb levels correlate with disease status and progression in PD patients.Identification of a potent, brain penetrant PINK1 activator, MTK458MTK458 selectively activates PINK1 by stimulating dimerization and stabilization of the PINK1/TOM complexMTK458 drives clearance of α-synuclein pathology and normalizes pUb in in vivo Parkinson's models.

Keyphrases

small molecule
end stage renal disease
newly diagnosed
ejection fraction
mouse model
inflammatory response