Summary
The findings of the research team have been recently published in the journal ‘Cell Reports Physical Science’
The inter-institutional team comprised researchers from IIT Mandi, University of Cambridge, UK, and University of South Florida, USA
A research team from the Indian Institute of Technology (IIT) Mandi led by Rajanish Giri, associate professor, School of Basic Sciences, IIT Mandi, have discovered an important biomolecular mechanism for the formation of protein clusters or aggregates that are often seen in Alzheimer’s disease.
They have shown that the signal peptide of the Amyloid Precursor Protein (APP) can co-aggregate with Amyloid beta peptide (Aβ42). This Aβ42, known for the pathogenesis of Alzheimer’s disease, a most common form of dementia that slowly destroys memory and other important mental functions.
While proteins are essential for virtually every process within the cell, their disturbed functions due to aggregation and/or misfolding can result in harmful effects. There are more than 50 diseases that are associated with protein aggregation or misfolding. Alzheimer’s disease, for example, is linked with the deposition of misfolded peptides called amyloid β42 (Aβ42) in the spaces between nerve cells. Aβ42 is a peptide derived from full-length protein Amyloid Precursor Protein (APP).
According to Giri, when proteins get aggregated or misfolded, they deposit around the cells and kill them, leading to the onset of many diseases. Until now, it was unknown whether signal peptides of amyloid precursor protein also have the tendency to form disease-causing aggregates.
The findings of the research team have been recently published in the journal ‘Cell Reports Physical Science’. The paper has been co-authored by Giri and his research scholars, Kundlik Gadhave and Taniya Bhardwaj, along with Michele Vendruscolo from the University of Cambridge, UK, and Vladimir Uversky from the University of South Florida, USA.
Speaking about his recent work, Giri said, “In Amyloid precursor protein, so far only the Aβ region was known to form toxic aggregates. Here, we discovered that Signal peptide of Amyloid precursor protein not only forms cell-killing aggregates but also enhances the aggregation of Aβ42 peptide, under in-vitro conditions.”
The inter-institutional team comprised researchers from IIT Mandi, University of Cambridge, UK, and University of South Florida, USA.
According to Giri this is the first report on an aggregation of signal peptides in isolation on the significance of their work. Their study shows a possible link between signal peptide aggregation and Alzheimer’s Aβ42 peptide aggregation.
This study will help in future research that could provide relation of other signal peptides to disease pathogenesis according to Giri on the future implications of this work.
Last updated on 23 Nov 2021
