A Novel, Selective c-Abl Inhibitor, Compound 5, Prevents Neurodegeneration in Parkinson's Disease.
Basic Information
ID: ALA4842381
Journal: J Med Chem
Title: A Novel, Selective c-Abl Inhibitor, Compound 5, Prevents Neurodegeneration in Parkinson's Disease.
Authors: Kwon SH, Kim S, Park AY, Lee S, Gadhe CG, Seo BA, Park JS, Jo S, Oh Y, Kweon SH, Ma SX, Kim WR, Kim M, Kim H, Kim JE, Lee S, Lee J, Ko HS.
Abstract: Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects movement. The nonreceptor tyrosine kinase c-Abl has shown a potential role in the progression of PD. As such, c-Abl inhibition is a promising candidate for neuroprotection in PD and α-synucleinopathies. Compound 5 is a newly synthesized blood-brain barrier penetrant c-Abl inhibitor with higher efficacy than existing inhibitors. The objective of the current study was to demonstrate the neuroprotective effects of compound 5 on the α-synuclein preformed fibril (α-syn PFF) mouse model of PD. Compound 5 significantly reduced neurotoxicity, activation of c-Abl, and Lewy body pathology caused by α-syn PFF in cortical neurons. Additionally, compound 5 markedly ameliorated the loss of dopaminergic neurons, c-Abl activation, Lewy body pathology, neuroinflammatory responses, and behavioral deficits induced by α-syn PFF injection in vivo. Taken together, these results suggest that compound 5 could be a pharmaceutical agent to prevent the progression of PD and α-synucleinopathies.
CiteXplore: 34583507
DOI: 10.1021/acs.jmedchem.1c01022
Patent ID: ┄