Impacts of nutrition and sleep on expression, solubility and functions of neural proteins.

Abstract

Scientific and technical advances in medicine and socioeconomic development contributed to the increase of life expectancy. On the other hand, aging of society has increased the prevalence of neurodegenerative diseases, while effective methods of treatment are not yet available. It is notable that the accumulation of protein aggregates is a common feature of many neurodegenerative diseases and in most cases, the aggregates form due to the spontaneous conformational alteration of a protein without mutations in corresponding genes. These findings raise a possibility of certain endogenous metabolites interacting with specific protein and inducing alterations in its structure. For example, dopamine has the ability to change protein structures by oxidative mechanisms, while the beta-amyloid peptide can seed hydrophobic interactions. The occurrence of both phenomena is highly dependent on their concentration. Certain habits or conditions of life such as sleep deprivation, chronic consumption of ketogenic diet or iron-restricted diet can alter the metabolism of dopamine and/or beta-amyloid peptide. The interest of our group is to investigate how the alteration of dopamine or beta-amyloid peptide metabolism established by these life conditions can affect the biochemical properties and functions of neural proteins. This proposal is based on the assumption that certain habits (or styles) of life can influence the activities and survival of neurons by changing the profile of endogenous metabolites. This study will be important not only for better understanding of neurodegeneration mechanisms, but also to seek preventive strategies for healthy aging. (AU)