Aß40 Aggregation under Changeable Conditions.

Homeostasis is crucial for cell function, and disturbances in homeostasis can lead to health disorders. Under normal conditions, intracellular pH is maintained between 7.35 and 7.45. Altered endosomal and lysosomal pH together with a general drop in brain pH are associated with the aggregation of amyloid-ß-peptide (Aß) and the development of Alzheimer's disease. Under acidic conditions, close to the Aß isoelectric point, the absence of charges favors the formation of intermolecular contacts and promotes aggregation. Here, we analyzed how pH levels affect the aggregation of Aß40 considering the variations in brain pH and the coexistence of different aggregated conformations. Our results suggest that different macromolecular conformations can interact with each other and influence the aggregation process. In addition, we showed that neutral pH and physiological salt concentrations favor a slow aggregation, resulting in ordered, stable fibrils, with low cytotoxic effects. Overall, we highlight the complexity of the aggregation processes occurring in different physiological and pathological environments.

Microbiome Impact on Amyloidogenesis.

Our life is closely linked to microorganisms, either through a parasitic or symbiotic relationship. The microbiome contains more than 1,000 different bacterial species and outnumbers human genes by 150 times. Worryingly, during the last 10 years, it has been observed a relationship between alterations in microbiota and neurodegeneration. Several publications support the hypothesis that amyloid structures formed by microorganisms may trigger host proteins aggregation. In this review, we collect pieces of evidence supporting that the crosstalk between human and microbiota amyloid proteins could be feasible and, probably, a more common event than expected before. The combination of their outnumbers, the long periods of time that stay in our bodies, and the widespread presence of amyloid proteins in the bacteria Domain outline a worrying scenario. However, the identification of the exact microorganisms and the mechanisms through with they can influence human disease also opens the door to developing a new and diverse set of therapeutic strategies.