Metabolic Dysfunction in Parkinson’s Disease: Unraveling the Glucose–Lipid Connection

Abstract

Despite many years of research into the complex neurobiology of Parkinson's disease, the precise aetiology cannot be pinpointed down to one causative agent but rather a multitude of mechanisms. Current treatment options can alleviate symptomsbut only slightly slow down the progression and not cure the disease and its underlying causes. Factors that play a role in causing the debilitating neurodegenerative psycho-motoric symptoms include genetic alterations, oxidative stress, neuroinflammation, general inflammation, neurotoxins, iron toxicity, environmental influences, and mitochondrial dysfunction. Recent findings suggest that the characteristic abnormal protein aggregation of alpha-synuclein and destruction of substantia nigra neurons might be due to mitochondrial dysfunction related to disturbances in lipid and glucose metabolism along with insulin resistance. The latter mechanism of action might be mediated by insulin receptor substrate docking to proteins that are involved in neuronal survival and signaling related to cell destruction. The increased risk of developing Type 2 Diabetes Mellitus endorses a connection between metabolic dysfunction and neurodegeneration. Here, we explore and highlight the potential role of glycolipid cellular insults in the pathophysiology of the disorder, opening up new promising avenues for the treatment of PD. Thus, antidiabetic drugs may be employed as neuromodulators to hinder the progression of the disorder.