A Novel Microtubule-Tau Association Enhancer and Neuroprotective Drug Candidate: Ac-SKIP

Ivashko-Pachima, Yanina and Gozes, Illana (2019) A Novel Microtubule-Tau Association Enhancer and Neuroprotective Drug Candidate: Ac-SKIP. Frontiers in Cellular Neuroscience, 13. ISSN 1662-5102

[thumbnail of pubmed-zip/versions/2/package-entries/fncel-13-00435-r1/fncel-13-00435.pdf] Text
pubmed-zip/versions/2/package-entries/fncel-13-00435-r1/fncel-13-00435.pdf - Published Version

Download (1MB)

Abstract

Activity-dependent neuroprotective protein (ADNP) has been initially discovered through its eight amino acid sequence NAPVSIPQ, which shares SIP motif with SALLRSIPA – a peptide derived from activity-dependent neurotrophic factor (ADNF). Mechanistically, both NAPVSIPQ and SALLRSIPA contain a SIP motif that is identified as a variation of SxIP domain, providing direct interaction with microtubule end-binding proteins (EBs). The peptide SKIP was shown before to provide neuroprotection in vitro and protect against Adnp-related axonal transport deficits in vivo. Here we show, for the first time that SKIP enhanced microtubule dynamics, and prevented Tau-microtubule dissociation and microtubule disassembly induced by the Alzheimer’s related zinc intoxication. Furthermore, we introduced, CH3CO-SKIP-NH2 (Ac-SKIP), providing efficacious neuroprotection. Since microtubule – Tau organization and dynamics is central in axonal microtubule cytoskeleton and transport, tightly related to aging processes and Alzheimer’s disease, our current study provides a compelling molecular explanation to the in vivo activity of SKIP, placing SKIP motif as a central focus for MT-based neuroprotection in tauopathies with axonal transport implications.

Item Type: Article
Subjects: Open Archive Press > Medical Science
Depositing User: Unnamed user with email support@openarchivepress.com
Date Deposited: 26 May 2023 05:33
Last Modified: 11 Mar 2024 05:22
URI: http://library.2pressrelease.co.in/id/eprint/1318

Actions (login required)

View Item
View Item