Evaluation of type 1 diabetes mellitus as a risk factor of Parkinson's disease in a Drosophila model.

Diabetes mellitus (DM) is a chronic metabolic disease characterized by high blood glucose levels, resulting from insulin dysregulation. Parkinson's disease (PD) is the most common neurodegenerative motor disorder caused by the selective loss of dopaminergic (DA) neurons in the substantia nigra pars compacta. DM and PD are both age-associated diseases that are turning into epidemics worldwide. Previous studies have indicated that type 2 DM might be a risk factor of developing PD. However, scarce information about the link between type 1 DM (T1DM) and PD does exist. In this work, we have generated a Drosophila model of T1DM based on insulin deficiency to evaluate if T1DM could be a risk factor to trigger PD onset. As expected, model flies exhibited T1DM-related phenotypes such as insulin deficiency, increased content of carbohydrates and glycogen, and reduced activity of insulin signaling. Interestingly, our results also demonstrated that T1DM model flies presented locomotor defects as well as reduced levels of tyrosine hydroxylase (a marker of DA neurons) in brains, which are typical PD-related phenotypes. In addition, T1DM model flies showed elevated oxidative stress levels, which could be causative of DA neurodegeneration. Therefore, our results indicate that T1DM might be a risk factor of developing PD, and encourage further studies to shed light into the exact link between both diseases.

Antioxidant and Neuroprotective Effects of Carnosine: Therapeutic Implications in Neurodegenerative Diseases.

Neurodegenerative diseases (NDs) constitute a global challenge to human health and an important social and economic burden worldwide, mainly due to their growing prevalence in an aging population and to their associated disabilities. Despite their differences at the clinical level, NDs share fundamental pathological mechanisms such as abnormal protein deposition, intracellular Ca2+ overload, mitochondrial dysfunction, redox homeostasis imbalance and neuroinflammation. Although important progress is being made in deciphering the mechanisms underlying NDs, the availability of effective therapies is still scarce. Carnosine is a natural endogenous molecule that has been extensively studied during the last years due to its promising beneficial effects for human health. It presents multimodal mechanisms of action, being able to exert antioxidant, anti-inflammatory and anti-aggregate activities, among others. Interestingly, most NDs exhibit oxidative and nitrosative stress, protein aggregation and inflammation as molecular hallmarks. In this review, we discuss the neuroprotective functions of carnosine and its implications as a therapeutic strategy in different NDs. We summarize the existing works that study alterations in carnosine metabolism in Alzheimer's disease and Parkinson's disease, the two most common NDs. In addition, we review the beneficial effect that carnosine supplementation presents in models of such diseases as well as in aging-related neurodegeneration.