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
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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 |
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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 |