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

Yanina Ivashko-Pachima, Illana Gozes*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number435
JournalFrontiers in Cellular Neuroscience
StatePublished - 1 Oct 2019


  • ADNP
  • EBs
  • SKIP
  • microtubules
  • tau


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