The sweet road to Parkinson’s disease

Long has functional neuroimagery exposed the importance of glucose in the fulfilment of the adult brain’s energetic needs. Actually, the brain utilizes 25% of total body glucose, mostly to power oxidative metabolism. However, the possible effects of hyperglycaemia on cerebral homeostasis are still contradictory. The clinical significance of hyperglycaemia in the brain emerged upon its formal identification as the prime culprit in comorbid diabetic complications [1]. The most affected collateral targets in diabetes mellitus are the kidneys, the cardiovascular system and the nervous system. Although it is clear that glucose concentrations rise in these cells under conditions of hyperglycaemia, how exactly cellular damage occurs is not as forthright. The current consensus is that oxidative stress explains hyper-glycaemia-induced diabetic complications [2]. Per se, oxidative stress arises from an imbalance between the generation and clearance of reactive oxygen species (ROS), in favor of the former, and may ultimately provoke cell death. This inability to cope with an oxidative overload constitutes a key pathological element, not only in hyperglycaemia, but also in Parkinson’s disease (PD) and aging. Indeed, it is now well appreciated that oxidative stress is a key player in the nigrostriatal degeneration observed in PD [3], a neurological condition affecting an estimated 1% of the population over the age of 60 years, making it the second most common neurodegenerative disorder after Alzheimer’s disease. PD pathology features a progressive loss of dopaminergic neurons harbored in the substantia nigra pars compacta (SNc) of the midbrain, which leads to decreased dopamine release in the dorsal striatum responsible for the emergence of motor impairments. The first accounts of a possible association between diabetes and PD date back to almost 60 years ago. Since then, other studies showed that diabetes exacerbates the progression of motor and cognitive deficits in PD and that drug-naïve parkinsonian patients display higher-than-normal levels of fasting blood glucose within the pre-diabetic diagnostic range [4]. Despite arduous efforts deployed to improve our understanding of the neuropathological underpinnings of PD, researchers are still at loss as to why the nigrostriatal dopaminergic pathway undergoes preferential early degeneration compared, for instance, to the neighEditorial