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.
Highlights
Protein misfolding disorders have become the main cause of various neurodegenerative diseases
In the last 40 years, as neurodegenerative-related diseases have become the major focus, it has been discovered that human brain cells are highly prone to the accumulation of misfolded/aggregated proteins [1,2], as they are deficient in some of the classical anti-oxidant and chaperone systems
The brain chaperone system consists of heat shock proteins (HSP),HSP70RY, HSP70.1, HSP 60, glucose regulated protein(GRP), GRP 75, GRP 78, GRP 94and Alpha-crystallin B
Summary
Protein misfolding disorders have become the main cause of various neurodegenerative diseases. The brain chaperone system consists of heat shock proteins (HSP),HSP70RY, HSP70.1, HSP 60, glucose regulated protein(GRP), GRP 75, GRP 78, GRP 94and Alpha-crystallin B, These chaperones are known to assist in modulating the apoptotic pathway and are involved in protein conformational disease pathologies. Brain cells house a number of small molecule compounds (osmolyte/osmoprotectant) that are believed to be involved in modulating proteo-stability or proteopathic conditions. Such a molecule comprises myo-inositol, glutamate, glutamine, creatine, and choline-containing compounds (e.g., glycerol phosphorylcholine) [3,4]. The results indicate that NAA is an important osmoprotectant and could be involved in the pathophysiology of Aβ, or alpha-synuclein-induced neurodegeneration
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