Chaperones-A New Class of Potential Therapeutic Targets in Alzheimer's Disease

• Published in: International journal of molecular sciences 2024-03, Vol.25 (6), p.3401
• Main Authors: Batko, Joanna, Antosz, Katarzyna, Miśków, Weronika, Pszczołowska, Magdalena, Walczak, Kamil, Leszek, Jerzy
• Format: Article
• Language: English
• Subjects: Advertising executives; Alzheimer Disease - metabolism; Alzheimer's disease; Amyloid beta-Peptides; Dementia; Development and progression; Disease; Exercise; Health aspects; Heat shock proteins; HSP70 Heat-Shock Proteins; HSP90 Heat-Shock Proteins - metabolism; Humans; Hypertension; Mediation; Molecular Chaperones - metabolism; Molecular weight; Oxidative stress; Polypeptides; Review
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25063401

The review describes correlations between impaired functioning of chaperones and co-chaperones in Alzheimer's disease (AD) pathogenesis. The study aims to highlight significant lines of research in this field. Chaperones like Hsp90 or Hsp70 are critical agents in regulating cell homeostasis. Due to some conditions, like aging, their activity is damaged, resulting in β-amyloid and tau aggregation. This leads to the development of neurocognitive impairment. Dysregulation of co-chaperones is one of the causes of this condition. Disorders in the functioning of molecules like PP5, Cdc37, CacyBP/SIPTRAP1, CHIP protein, FKBP52, or STIP1 play a key role in AD pathogenesis. PP5, Cdc37, CacyBP/SIPTRAP1, and FKBP52 are Hsp90 co-chaperones. CHIP protein is a co-chaperone that switches Hsp70/Hsp90 complexes, and STIP1 binds to Hsp70. Recognition of precise processes allows for the invention of effective treatment methods. Potential drugs may either reduce tau levels or inhibit tau accumulation and aggregation. Some substances neuroprotect from Aβ toxicity. Further studies on chaperones and co-chaperones are required to understand the fundamental tenets of this topic more entirely and improve the prevention and treatment of AD.