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REVIEW article

Front. Mol. Neurosci.
Sec. Brain Disease Mechanisms
Volume 17 - 2024 | doi: 10.3389/fnmol.2024.1509280

The Role of Aha1 in Cancer and Neurodegeneration

Provisionally accepted
Brian Blagg Brian Blagg *kevin catalfano kevin catalfano
  • University of Notre Dame, Notre Dame, United States

The final, formatted version of the article will be published soon.

    The 90 kDa Heat shock protein (Hsp90) is a family of ubiquitously expressed molecular chaperones responsible for the stabilization and maturation of >400 client proteins. Hsp90 exhibits dramatic conformational changes to accomplish this, which are regulated by partner proteins termed co-chaperones. One of these co-chaperones is called the activator or Hsp90 ATPase activity homolog 1 (Aha1) and is the most potent accelerator of Hsp90 ATPase activity. 1–4 In conditions where Aha1 levels are dysregulated including cystic fibrosis, cancer and neurodegeneration, Hsp90 mediated client maturation is disrupted. Accumulating evidence has demonstrated that many disease states exhibit large hetero-protein complexes with Hsp90 as the center. Many of these include Aha1, where increased Aha1 levels drive disease states forward. One strategy to block these effects is to design small molecule disruptors of the Hsp90/Aha1 complex. Studies have demonstrated that current Hsp90/Aha1 small molecule disruptors are effective in both models for cancer and neurodegeration

    Keywords: Hsp90, Aha1, cancer, tauopathy, protein-protein interaction, small molecule 90 kDa Heat shock protein, Hsp90, Activator of Hsp90 ATPase Activity Homolog 1, Aha1, AHSA1, Alzheimer's disease, AD, Amyloid beta, ALS, Aryl hydrocarbon receptor, AH, Caldesomon, CALD1, Carboxyl terminal domain, CTD, Carboxyl terminus of Hsc70-interacting protein

    Received: 11 Oct 2024; Accepted: 06 Dec 2024.

    Copyright: © 2024 Blagg and catalfano. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Brian Blagg, University of Notre Dame, Notre Dame, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.