Regulation of Blos1 by IRE1 prevents the accumulation of Huntingtin protein aggregates.

Huntington's disease is characterized by accumulation of the aggregation-prone mutant Huntingtin (mHTT) protein. Here, we show that expression of exon 1 of mHTT in mouse cultured cells activates IRE1, the transmembrane sensor of stress in the endoplasmic reticulum, leading to degradation of the Blos1 mRNA and repositioning of lysosomes and late endosomes toward the microtubule organizing center. Overriding Blos1 degradation results in excessive accumulation of mHTT aggregates in both cultured cells and primary neurons. Although mHTT is degraded by macroautophagy when highly expressed, we show that before the formation of large aggregates, mHTT is degraded via an ESCRT-dependent, macroautophagy-independent pathway consistent with endosomal microautophagy. This pathway is enhanced by Blos1 degradation and appears to protect cells from a toxic, less aggregated form of mHTT.

Accelerated identification of serine racemase inhibitor from Centella asiatica.

Serine racemase (SR) converts the free form of L-serine into D-serine (DS) in the mammalian brain. The DS functions as a co-agonist of N-methyl D-aspartate (NMDA) receptor. The over- activation of NMDA receptor leads to many neurological disorders like stroke, amyotrophic lateral sclerosis, Alzheimer's disease and an effective inhibitor of SR could be a corrective method for the receptor over-activation. We report for the first time here a rapid way of purifying and identifying an inhibitor from medicinal plants known to have the neuro-protective effect. We have purified SR inhibitor from the methanolic extract of Centella asiatica by affinity method. High resolution mass spectrometry and infrared spectroscopy were used to identify the ligand to be madecassoside. We have shown the madecassoside binding in silico and its inhibition of recombinant human serine racemase in vitro and ex vivo.

Publisher Correction: Characterization of protein extracts from different types of human teeth and insight in biomineralization.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Characterization of protein extracts from different types of human teeth and insight in biomineralization.

The present study describes an efficient method for isolation and purification of protein extracts from four types of human teeth i.e. molar, premolar, canine, and incisor. Detailed structural characterization of these protein extracts was done by Fourier transform infrared spectroscopy (FTIR) and circular dichroism (CD) which showed that a major fraction of the proteins present are unstructured in nature including primarily random coils in addition to the other structures like extended beta (ß) structure, poly-l-proline-type II (PPII) helix, turns, with only a small fraction constituting of ordered structures like alpha (α) helix and ß sheets. These resultant labile structures give the proteins the necessary flexibility that they require to interact with a variety of substrates including different ions like calcium and phosphates and for other protein-protein interactions. We also did initial studies on the mineralization of calcium phosphate with the protein extracts. Nanoparticle tracking analysis (NTA) show an increase in the size of calcium phosphate accumulation in the presence of protein extracts. We propose that protein extracts elevate the crystallization process of calcium phosphate. Our current biophysical study provides novel insights into the structural characterization of proteins from human teeth and their implications in understanding the tooth biomineralization. As per our knowledge, this is the first report which focuses on the whole protein extraction from different types of human teeth as these extracts imitate the in vivo tooth mineralization.