Targeting glucose transporters in parkinson's disease: a novel metabolic approach for disease modification

Glucose metabolism is vital for maintaining the effective functioning of the central nervous system (CNS). This energy supports synaptic activity, ion balance, and neurotransmitter synthesis, processes that depend on the GLUTs (glucose transporters), particularly GLUT1(Glucose transporter 1), GLUT2(Glucose transporter 2), and GLUT3 (Glucose transporter 3). There is growing evidence associating GLUT deficiency and metabolic disorders with neurodegenerative diseases, including Parkinson's disease (PD). PD is a progressive neurodegenerative disease linked with the degeneration of dopaminergic neurons in the SNpc, resulting in impaired motor and non-motor functions. More than 60% of patients with PD show glucose intolerance and insulin resistance, emphasizing the relation between metabolic disturbances and disease progression. The reduced expression of these GLUTs further restricts the neuronal glucose uptake, impairing ATP production and increasing liability to oxidative damage, leading to disease progression. Emerging finding suggests that targeting GLUT offers a therapeutic strategy for PD. Restoring GLUT function may help to reduce energy deficits and have neuroprotective effects. Several antidiabetic drugs have shown promise in reducing the symptoms and development of PD in both human and animal models. This narrative review addresses the current understanding of the connection between GLUT dysfunction and PD, highlighting the potential of targeting GLUT dysregulation as a novel therapeutic strategy. Additionally, repurposing antidiabetic drugs shows promise in improving insulin sensitivity and reducing neuroinflammation in PD. Addressing challenges like GLUT isoform specificity and BBB penetration provides a way for disease-modifying therapies that target GLUT dysfunction in PD, offering hope for effective management or reducing the rate of PD's progression.