Bozuk Mitokondriyal ve Metabolik Plastisite Parkinson Hastalığı ve Tip 2 Diyabet Mellitus Olarak Yaşa Bağlı ve Dejeneratif Bozukluklar Arasındaki Komorbiditenin Altında

Araştırma özeti

Aşağıdaki metin kaynak makalenin lisansı doğrulanmış orijinal özetidir. cc by

Abstract Background. Idiopathic Parkinson’s disease (iPD) and Type 2 Diabetes Mellitus (T2DM) are chronic, degenerative, multisystemic and age-related diseases, with eventual epidemiological co-morbidity and potential overlap in molecular basis. This study aims to explore if metabolic and mitochondrial alterations underlie the suggested epidemiologic and clinical co-morbidity at molecular level. Methods. To evaluate the adaptation of iPD to a simulated pre-diabetogenic state, we exposed primary cultured fibroblasts from iPD patients and controls to standard (5mM) and high (25mM) glucose concentrations to further characterize metabolic and mitochondrial resilience.Results. iPD fibroblasts showed increased levels of organic and amino acid levels related to mitochondrial metabolism with respect to controls, and these differences were enhanced in high glucose conditions (citric, suberic and sebacic acids levels increased, as well as alanine, glutamate, aspartate, arginine and ornithine amino acids; p-values between 0.001 and p=0.05). The accumulation of metabolites in iPD fibroblasts was associated (and probably due) to the concomitant mitochondrial dysfunction observed at enzymatic, oxidative, respiratory and morphologic level. Metabolic and mitochondrial plasticity of controls was not observed in iPD fibroblasts, that were unable to adapt to different glucose conditions. Impaired metabolism and mitochondrial activity in iPD may limit energy supply for cell survival. Moreover, deficient plasticity to adapt to disrupted glucose balance characteristic of T2DM may underlay the comorbidity between both diseases. Conclusions:Fibroblasts form iPD patients showed mitochondrial impairment resulting in the accumulation of organic and amino acids related to mitochondrial metabolism, especially when exposed to high glucose condition. Mitochondrial and metabolic defects down warding cell plasticity to adapt to changing glucose bioavailability may explain the comorbidity between iPD and T2DM.

İlgili konular