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Purpose of review <p>Alzheimer’s disease (AD) is a chronic neurodegenerative condition characterized by β-amyloid (Aβ) accumulation, tau hyperphosphorylation, and progressive cognitive deterioration. Despite decades of research, effective long-term treatments remain elusive. This review examines the role of heat shock proteins (HSPs), particularly HSP70 and HSP90, in the pathogenesis of AD and evaluates the therapeutic potential of modulating their activity. Special attention is given to the emerging contributions of Traditional Chinese Medicine (TCM) in regulating HSP function as a multi-targeted approach to AD management.</p> Recent findings <p>Heat shock proteins are essential molecular chaperones involved in maintaining cellular proteostasis, especially under pathological stress. Increasing evidence implicates dysregulation of HSP70 and HSP90 in AD progression, where their impaired activity may contribute to protein misfolding, aggregation, and neuronal loss. Recent studies have demonstrated that pharmacological or natural modulation of HSP expression can attenuate Aβ deposition, reduce tau pathology, and mitigate synaptic dysfunction. In this context, TCM formulations and active constituents have shown promising capabilities to modulate HSP activity through diverse biochemical pathways, often with low toxicity and systemic compatibility. These findings suggest that TCM-based modulation of HSPs may offer a novel therapeutic route to interfere with multiple aspects of AD pathology simultaneously.</p> Summary <p>HSPs represent a compelling therapeutic target in AD due to their central role in protein homeostasis and neuroprotection. The ability of TCM to influence HSP expression and activity highlights its potential as a holistic and multi-modal intervention. A better understanding of the interplay between HSPs and TCM-based compounds may contribute to the development of innovative and more effective treatment strategies for AD. Further research into this integrative approach could lead to improved therapeutic outcomes and provvide a valuable complement to existing pharmacological interventions.</p> Graphical abstract <p></p>

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Therapeutic Application of Traditional Chinese Medicine Targeting Heat Shock Proteins in Alzheimer’s Disease

  • 期刊论文

  • 发表日期：

    2025年6月4日

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  • Yang Pan,
  • Youqian Kong,
  • Xiaoyu Wang,
  • Nan Li,
  • Hechen Sun,
  • Rui Qie

摘要

Purpose of review

Alzheimer’s disease (AD) is a chronic neurodegenerative condition characterized by β-amyloid (Aβ) accumulation, tau hyperphosphorylation, and progressive cognitive deterioration. Despite decades of research, effective long-term treatments remain elusive. This review examines the role of heat shock proteins (HSPs), particularly HSP70 and HSP90, in the pathogenesis of AD and evaluates the therapeutic potential of modulating their activity. Special attention is given to the emerging contributions of Traditional Chinese Medicine (TCM) in regulating HSP function as a multi-targeted approach to AD management.

Recent findings

Heat shock proteins are essential molecular chaperones involved in maintaining cellular proteostasis, especially under pathological stress. Increasing evidence implicates dysregulation of HSP70 and HSP90 in AD progression, where their impaired activity may contribute to protein misfolding, aggregation, and neuronal loss. Recent studies have demonstrated that pharmacological or natural modulation of HSP expression can attenuate Aβ deposition, reduce tau pathology, and mitigate synaptic dysfunction. In this context, TCM formulations and active constituents have shown promising capabilities to modulate HSP activity through diverse biochemical pathways, often with low toxicity and systemic compatibility. These findings suggest that TCM-based modulation of HSPs may offer a novel therapeutic route to interfere with multiple aspects of AD pathology simultaneously.

Summary

HSPs represent a compelling therapeutic target in AD due to their central role in protein homeostasis and neuroprotection. The ability of TCM to influence HSP expression and activity highlights its potential as a holistic and multi-modal intervention. A better understanding of the interplay between HSPs and TCM-based compounds may contribute to the development of innovative and more effective treatment strategies for AD. Further research into this integrative approach could lead to improved therapeutic outcomes and provvide a valuable complement to existing pharmacological interventions.

Graphical abstract