Hsp90-interacting Co-chaperones and their Family Proteins in Tau Regulation: Introducing a Novel Role for Cdc37L1

Tau is a microtubule-associated protein that serves as a promoter of microtubule assembly and stability in neuron cells. In a collective group of neurodegenerative diseases called tauopathies, tau processing is altered as a result of gene mutations and post-translational modifications. In particular, in Alzheimer's disease (AD) or AD-like conditions, tau becomes hyperphosphorylated and forms toxic aggregates inside the cell. The chaperone heat shock protein 90 (Hsp90) plays an important role in the proper folding, degradation, and recycling of tau proteins and tau kinases. Hsp90 has many co-chaperones that aid in tau processing. In particular, a few of these co-chaperones, such as FK506-binding protein (FKBP) 51, protein phosphatase (PP) 5, cell division cycle 37 (Cdc37), and S100A1 have family members that are reported to affect Hsp90-mediated tau processing in either a similar or an opposite manner. Here, we provide a holistic review of these selected co-chaperones and their family proteins and introduce a novel Hsp90-binding Cdc37 relative, Cdc37-like-1 (Cdc37L1 or L1) in tau regulation. Overall, the proteins discussed here highlight the importance of studying family proteins in order to fully understand the mechanism of tau pathogenesis and to establish drug targets for the treatment of tauopathies. Published by Elsevier Ltd on behalf of IBRO.

Automated summary

Tau is a microtubule-associated protein involved in promoting microtubule assembly and stability in neuron cells, but its processing can be altered in tauopathies due to gene mutations and post-translational modifications. The chaperone heat shock protein 90 (Hsp90) plays a crucial role in the folding, degradation, and recycling of tau proteins and tau kinases. The study also discusses the impact of various co-chaperones, such as FK506-binding protein 51, on Hsp90-mediated tau processing.