Mitochondrial unfolded protein response (UPR) 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) is an evolutionarily conserved mitochondrial response, which is critical for maintaining mitochondrial and energetic homeostasis under stress. Previous studies have found that UPR participates in diverse physiological processes especially metabolism and immunity. Currently, increasing evidence suggest that targeted regulation of UPR can also effectively delay the progression of neurological diseases and improve patients' prognosis. This review provides a comprehensive overview of UPR in the context of neurological diseases, with a particular emphasis on its regulatory functions. Additionally, we summarize the mechanistic insights into UPR 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 in the complex processes underlying neurological disorders, this review aims to bridge current knowledge gaps and inspire novel therapeutic strategies for these conditions.