Mitochondrial dysfunction plays a key role in the development of neurodegenerative diseases in diabetes.

Mitochondria have an essential function in cell survival due to their role in bioenergetics, reactive oxygen species generation, calcium buffering, and other metabolic activities. Mitochondrial dysfunctions are commonly found in neurodegenerative diseases (NDs), and diabetes is a risk factor for NDs. However, the role of mitochondria in diabetic neurodegeneration is still unclear. In the present study, we review the latest evidence on the role of mitochondrial dysfunctions in the development of diabetes-related NDs and the underlying molecular mechanisms. Hypoglycemic agents, especially metformin, have been proven to have neuroprotective effects in the treatment of diabetes, in which mitochondria could act as one of the underlying mechanisms. Other hypoglycemic agents, including thiazolidinediones (TZDs), dipeptidyl peptidase 4 (DPP-4) inhibitors, and glucagon-like peptide 1 (GLP-1) receptor agonists, have gained more attention because of their beneficial effects on NDs, presumably by improving mitochondrial function. Our review highlights the notion that mitochondria could be a promising therapeutic target in the treatment of NDs in patients with diabetes.