Targeting the Mitochondrion in Diabetic Neuropathy

Abstract

Dysfunction of mitochondria and signaling pathways related to their function can lead to diabetic peripheral neuropathy, and understanding these mechanisms is key to developing new therapies. Though the pathophysiology of diabetic neuropathy (DN) is complex, specific pathways that regulate mitochondrial function are potential targets for therapy. Oxidative stress and nitrosative stress trigger several pathways that induce neuroinflammation associated with the pathophysiology of diabetic neuropathy. Mitochondrial dysfunction in neurons and axons is amplified by aberrant glycemic and hyperlipidemic metabolism resulting in abnormal DNA structure and protein generation. Mitochondrial function can be regulated by transcription factors such as SIRT1, PGC-1α, and TFAM upregulation of these transcription factors improves diabetic neuropathy. Nrf2, which facilitates the expression of several antioxidant proteins via antioxidant response element (ARE) binding sites, affects the progression of diabetic neuropathy. Other pathways that modulate injury to the peripheral nerve are TGF-β, AGEs, glyoxalase 1, PKC, and molecular chaperones. Potential mitochondrial-related pathways that can be targeted for treatment are discussed.