Research Progress on How Multimodal Signals Regulate Neuronal Mitochondrial Homeostasis to Affect Diabetic Cognitive...

Diabetic cognitive impairment (DCI) affects approximately 25%-35% of patients with diabetes and is characterized by progressive cognitive decline. Dysfunction of mitochondria-the energy factories within neurons-is considered a potential pathogenic factor of DCI, involving processes such as oxidative stress, calcium overload, autophagic dysfunction, and genetic mutations, ultimately disrupting normal neuronal function. Maintaining mitochondrial quality and function is critical for neuronal health. Recent studies have shown that there are multiple ways in which cells can communicate signals, such as extracellular vesicles (EVs), tunneling nanotubes and gap junctions, which can repair and replace damaged mitochondria within receptor cells. Notably, EV-mediated mitochondrial transplantation has demonstrated significant potential by transferring healthy mitochondria to impaired neurons and restoring energy metabolism and antioxidant defences, thereby offering novel therapeutic strategies for intervening in DCI progression with valuable clinical translation potential. This review systematically elucidates multimodal signalling strategies targeting mitochondrial homeostasis, with a focused analysis on the role of EV-mediated mitochondrial transplantation in restoring neuronal energy balance, providing a theoretical foundation for the development of innovative DCI interventions.