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

Randall M Chin, Rishi Rakhit,Dara Ditsworth,Chengzhong Wang, Johan Bartholomeus,Song Liu,Akash Mody, Alex Laishu,Andrea Eastes, Chao Tai,Roy Y Kim, Jessica Li,Steven Hansberry, Saurabh Khasnavis, Victoria Rafalski, Donald Herendeen,Virginia Garda, Jennie Phung, Daniel de Roulet,Alban Ordureau,J Wade Harper, Shawn Johnstone,Jan Stöhr,Nicholas T Hertz

biorxiv（2023）

引用 7|浏览12

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摘要

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.

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pharmacological pink1 activation,parkinsons

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