RESUMO
Neurodegenerative diseases (NDs), such as Alzheimer's (AD), Parkinson's (PD), and amyotrophic lateral sclerosis (ALS), share common pathological mechanisms, including metabolism alterations. However, their specific neuronal cell types affected and molecular biomarkers suggest that there are both common and specific alterations regarding metabolite levels. In this review, we were interested in identifying metabolite alterations that have been reported in preclinical models of NDs and that have also been documented as altered in NDs patients. Such alterations could represent interesting targets for the development of targeted therapy. Importantly, the translation of such findings from preclinical to clinical studies is primordial for the study of possible therapeutic agents. We found that N-acetyl-aspartate (NAA), myo-inositol, and glutamate are commonly altered in the three NDs investigated here. We also found other metabolites commonly altered in both AD and PD. In this review, we discuss the studies reporting such alterations and the possible pathological mechanism underlying them. Finally, we discuss clinical trials that have attempted to develop treatments targeting such alterations. We conclude that the treatment combination of both common and differential alterations would increase the chances of patients having access to efficient treatments for each ND.
RESUMO
BACKGROUND: The study of clinically related biological indicators in Major Depression (MD) is important. The Brain Derived Neurotrophic Factor (BDNF) appears to play an important role in MD, through its neurotrophic effect, and its levels are significantly decreased. The variation in the serum levels of its precursor proBDNF, which has opposite effects, is not known. Their distribution between serum and exosomes and their evolution during antidepressant treatment is also not known, and may be important in modulating their effects. The aim of this study is to evaluate whether serum and exosome mBDNF and proBDNF levels are altered in patients with MD during antidepressant treatment compared to controls, and their association with clinical improvement and clinical variables. MATERIALS AND METHODS: 42 MD subjects and 40 controls were included. Questionnaires to assess the severity of depression and cognitive impairment and blood samples were collected during the three visits at D0 (inclusion) and 3 and 7 weeks after the start of antidepressant treatment. Assays for mBDNF and proBDNF levels were performed in serum and exosomes by ELISA. RESULTS: MD subjects had decreased serum and exosomal BDNF levels and increased proBDNF levels at D0 compared to controls. BDNF and pro-BDNF vary in an inverse manner in both serum and exosomes during antidepressant treatment. No relationship of BDNF and proBDNF levels to clinical improvement and depression scales was found. CONCLUSION: We demonstrated an evolution of those molecules either in serum or in exosomes after MD treatment. These transport vesicles could have a role in the regulation of BDNF.
