Pharmacol Ther. 2026 Aug 21:109101. doi: 10.1016/j.pharmthera.2026.109101. Online ahead of print.
ABSTRACT
Neurodegenerative diseases have emerged as a significant global health challenge, with existing treatments merely providing symptomatic relief and failing to halt disease progression. Mitochondrial dysfunction and an imbalance in the molecular chaperone network constitute the core common pathological mechanisms underlying various neurodegenerative diseases (NDDs). These two factors collaboratively induce energy metabolism disorders, oxidative stress, calcium homeostasis imbalance, and protein homeostasis collapse, collectively driving neuronal degeneration. This article systematically elucidates the core characteristics of mitochondrial dysfunction in NDDs, dissects the molecular mechanisms by which the mitochondrial molecular chaperone network maintains mitochondrial homeostasis, summarizes therapeutic strategies for NDDs aimed at restoring mitochondrial and related molecular chaperone functions, discusses the current challenges faced in research, such as targeted delivery and clinical translation, and also proposes potential development directions for future.
PMID:42628807 | DOI:10.1016/j.pharmthera.2026.109101