Amyotrophic lateral sclerosis (ALS) is a multifactorial and progressive neurodegenerative disease of unknown etiology. Due to ALS’s unpredictable onset and progression rate, the search for biomarkers that allow the detection and tracking of its development and therapeutic efficacy would be of significant medical value. Considering that alterations of energy supply are one of ALS’s main hallmarks and that a correlation has been established between gene expression in human brain tissue and peripheral blood mononuclear cells (PBMCs), the present work investigates whether changes in mitochondrial function could be used to monitor ALS. To achieve this goal, PBMCs from ALS patients and control subjects were used; blood sampling is a quite non-invasive method and is cost-effective. Different parameters were evaluated, namely cytosolic calcium levels, mitochondrial membrane potential, oxidative stress, and metabolic compounds levels, as well as mitochondrial dynamics and degradation. Altogether, we observed lower mitochondrial calcium uptake/retention, mitochondria depolarization, and redox homeostasis deregulation, in addition to a decrease in critical metabolic genes, a diminishment in mitochondrial biogenesis, and an augmentation in mitochondrial fission and autophagy-related gene expression. All of these changes can contribute to the decreased ATP and pyruvate levels observed in ALS PBMCs. Our data indicate that PBMCs from ALS patients show a significant mitochondrial dysfunction, resembling several findings from ALS’ neural cells/models, which could be exploited as a powerful tool in ALS research. Our findings can also guide future studies on new pharmacological interventions for ALS since assessments of brain samples are challenging and represent a relevant limited strategy.

Background: The development of strategies that could not only efficiently detect the onset of Amyotrophic Lateral Sclerosis (ALS), a fatal neurodegenerative disorder with no cure but also predict its development and evaluate therapeutic intervention would be of great value. In this respect, the metabolic status of ALS patients has called attention. Hence, this study aimed to investigate the potential correlation between changes in ALS's metabolic parameters with the disease outcome in a systematic review.Methods: The manuscripts were manually searched within different databases (PubMed, Web of Science and Cochrane). The inclusion criteria were original articles and reviews about individuals with ALS and its survival, disease prognosis and metabolism (weight, cholesterol, hypertension, BMI, and glycaemia). The authors also established three different exclusion criteria: studies including ALS and other degenerative disorders, works including animal models and published before the year 2000.Results: In total, 29 papers were selected. From all manuscripts, only 82.8% ensured the participation of sALS patients. Also, 27.6% of selected studies described the presence of a genetic mutation. Regarding ALS prognosis, patient's age, the age of ALS onset, ALS duration and survival, <50% of the papers addressed these issues. Specifically, regarding metabolism, 65.5% of articles mentioned BMI, 20.7% mentioned any data concerning hypertension, 6.89% cardiovascular risk, 10.3% obesity, 13.78% diabetes and 10.3% glycaemia. Concerning lipid metabolism, more results were gathered, but still, they did not suffice to establish a correlation with ALS development.Conclusions: Altogether, the authors concluded that available information is not enough to establish a link between ALS and metabolism. In reality, less than half of the manuscripts evaluated show an association between both factors. Nonetheless, it is worth mentioning that metabolism does influence ALS, but not in a unique manner. There is a debate about patients' hypo- and hypermetabolism. Thus, to provide a reliable record, a public policy in which all research and clinical centers might assess the parameters discussed herein is suggested. Accordingly, this systematic review attempts to provide a comprehensible database to facilitate multicentered collaboration, validation, and clinical translation.

Hygiene hypothesis dictates that the lack of microbial interaction during the first childhood increases the chance of developing autoimmune diseases due to not proper immune system maturation. Helminthes are known by their Th2 and modulatory immune response induction. Here, it was evaluated the influence of Necator americanus antigens during type 1 experimental mouse model (non-obese diabetic -NOD). Intraperitoneal injections for 18 weeks did not impair an inflammatory response, but induced a mixed Th1/Th2 response with presence of IL4 and IL10 from different sources. However, the induced immune response was not sufficient to decrease glucose levels but showed a change in the inflammatory infiltrate in the pancreas. It is necessary more refined studies to clarify the mechanisms of how Necator americanus could impair diabetes progression in mice.