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Conformational Dynamics of Hsp90 and Hsp70 Chaperones in Treating Neurodegenerative Diseases: Insights from the Drosophila Model

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Protein aggregates of misfolded proteins are a pathological hallmark of nearly all neurological disorders, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and various polyglutamine diseases such as Huntington’s disease. Selective distribution in different cellular compartments highlights their core functions in cellular homeostasis. Investigating the cellular protein quality control system has become a significant strategy for counteracting protein aggregates and their toxic consequences. Heat shock proteins (Hsps) are crucial in regulating protein quality control, contributing to both protein aggregation and disaggregation. Beyond their well-known role in oncogenesis, several studies have identified Hsp90 as a key regulator of the functional stability of neuronal proteins. Similarly, Hsp70 is believed to promote cell survival by interacting with components of apoptotic and pro-survival pathways in neurodegeneration. Thus, targeting Hsp90 and Hsp70 represents a promising therapeutic strategy for treating neurodegenerative disorders. This review provides a comprehensive overview of the structure, mode of action, and roles of Hsp90 and Hsp70. Additionally, Drosophila melanogaster is highlighted as an effective model system for studying the roles of Hsp70 and Hsp90 in the proteinopathies associated with neurodegenerative diseases.

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Acknowledgements

I extend my sincere gratitude to Prof. J.K. Roy of the Cytogenetics Laboratory, Department of Zoology, Institute of Science, Banaras Hindu University, India, and Prof. Andreas Bergmann of the Department of Molecular, Cell, and Cancer Biology, University of Massachusetts Medical School, USA, for their invaluable support in understanding fly genetics. I also thank Sonam Sriwastaw (SR) from the Department of Botany, Banaras Hindu University, for her assistance with protein structural analysis. Additionally, I appreciate the University Grants Commission, New Delhi, for providing a fellowship to PR (598/OBC-CSIR UGC NET-DEC 2016).

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    Present address: Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, MA, 01655, USA

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  1. Cytogenetics Laboratory, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, 221005, India

    Pooja Rai

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Rai, P. Conformational Dynamics of Hsp90 and Hsp70 Chaperones in Treating Neurodegenerative Diseases: Insights from the Drosophila Model. Proc.Indian Natl. Sci. Acad. 90, 628–637 (2024). https://doi.org/10.1007/s43538-024-00325-7

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