Parkinson Disease-Modification Encompassing Rotenone and 6-Hydroxydopamine Neurotoxicity by the Microtubule-Protecting Drug Candidate SKIP

Yanina Ivashko-Pachima, Kim B. Seroogy, Yehonatan Sharabi, Illana Gozes

Research output: Contribution to journalEditorial

Abstract

Encompassing live cell imaging and morphometrics at the microscopical level, we showed here, for the first time, protection of neuronal-like cells by the novel drug candidate, SKIP, against the Parkinson’s disease-related neurotoxin, rotenone. Mechanistically, rotenone disrupted microtubule dynamics, which SKIP partially repaired through microtubule end-binding proteins, coupled with increasing neurite branch length. Given the previous association of rotenone toxicity with increased dopaminergic cell death hallmarking Parkinson’s disease, we chose an established rat model of 6-hydroxydopamine (6-OHDA) toxicity to initially evaluate SKIP in vivo. SKIP pretreatment showed protection against nigral dopaminergic cell degeneration and improved motor behavior in the forelimb asymmetry test. With Parkinson’s disease being a major neurodegenerative disorder, afflicting millions of people globally, and with disease modification challenges, SKIP may hold promise for future therapeutic development.

Original languageEnglish
Pages (from-to)1515-1524
Number of pages10
JournalJournal of Molecular Neuroscience
Volume71
Issue number8
DOIs
StatePublished - Aug 2021

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