Mitochondrial unfolded protein response (UPR^mt) as novel therapeutic targets for neurological disorders

Neurological disorders, including brain cancer, neurodegenerative diseases and ischemic/reperfusion injury, pose a significant threat to global human health. Due to the high metabolic demands of nerve cells, mitochondrial dysfunction is a critical feature of these disorders. The mitochondrial unfolded protein response (UPR^mt) is an evolutionarily conserved mitochondrial response, which is critical for maintaining mitochondrial and energetic homeostasis under stress. Previous studies have found that UPR^mt participates in diverse physiological processes especially metabolism and immunity. Currently, increasing evidence suggest that targeted regulation of UPR^mt can also effectively delay the progression of neurological diseases and improve patients' prognosis. This review provides a comprehensive overview of UPR^mt in the context of neurological diseases, with a particular emphasis on its regulatory functions. Additionally, we summarize the mechanistic insights into UPR^mt in neurological disorders as investigated in preclinical studies, as well as its potential as a therapeutic target in the clinical management of neurological tumors. By highlighting the importance of UPR^mt in the complex processes underlying neurological disorders, this review aims to bridge current knowledge gaps and inspire novel therapeutic strategies for these conditions.