N-Acetylaspartate Is an Important Brain Osmolyte

Abstract

Most of the human diseases related to various proteopathies are confined to the brain, which leads to the development of various forms of neurological disorders. The human brain consists of several osmolytic compounds, such as N-Acetylaspartate (NAA), myo-inositol (mI), glutamate (Glu), glutamine (Gln), creatine (Cr), and choline-containing compounds (Cho). Among these osmolytes, the level of NAA drastically decreases under neurological conditions, and, hence, NAA is considered to be one of the most widely accepted neuronal biomarkers in several human brain disorders. To date, no data are available regarding the effect of NAA on protein stability, and, therefore, the possible effect of NAA under proteopathic conditions has not been fully uncovered. To gain an insight into the effect of NAA on protein stability, thermal denaturation and structural measurements were carried out using two model proteins at different pH values. The results indicate that NAA increases the protein stability with an enhancement of structure formation. We also observed that the stabilizing ability of NAA decreases in a pH-dependent manner. Our study indicates that NAA is an efficient protein stabilizer at a physiological pH.

Effects of ‘Healthy’ Fecal Microbiota Transplantation against the Deterioration of Depression in Fawn-Hooded Rats

“…The increase in nitrogen-rich metabolites in serum may translate to the brain through the BBB, increasing amino acids synthesis in the hippocampus (e.g., serine) and decreasing the concentration of brain osmolytes (e.g., NAA). The level of hippocampal NAA has been noted in several human brain disorders ( 34 , 35 ). Even though its functional roles remain unclear, it is believed to be involved in neuromodulation, which is supported by one interpretation of the results presented here.…”

Brain Metabolite, N-Acetylaspartate Is a Potent Protein Aggregation Inhibitor

“…It has been known from various studies that NAA is an osmolyte in the brain cells responsible for the removal of water from neurons (Taylor et al, 1994(Taylor et al, , 1995. Most recently, our laboratory also reported that NAA exhibit strong stabilizing effect on different proteins (due to increase in T m and G D • ) (Warepam et al, 2020). Furthermore as mentioned above, there is alteration in the NAA levels under various neurodegenerative conditions.…”

Amelioration of depressive symptoms on Fawn-Hooded rats through the 'healthy' fecal microbiota transplantation

“…The increase in nitrogen-rich metabolites in serum may translate to the brain through the BBB, increasing amino acids synthesis in hippocampus (e.g., serine) and decreasing the concentration of brain osmolytes (e.g., NAA). The level of hippocampal NAA has been noted in several human brain disorders 34,35 . Even though its functional roles remain unclear, it is believed to be involved in neuromodulation, which is supported by one interpretation of the results presented here.…”