A research team from the Indian Institute of Technology Mandi led by Dr. Rajanish Giri, Associate Professor, School of Basic Sciences, IIT Mandi, have discovered an important biomolecular mechanism for the formation of protein clusters/aggregates that are often seen in Alzheimer’s disease. They have shown that 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/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).

Generally, when proteins get aggregated or misfolded , they deposit around the cells and kills them, leading to the onset of many diseases. Till now, it was unknown whether signal peptide of amyloid precursor protein also have the tendency to form disease-causing aggregates? Can signal peptide co-assemble with the Alzheimer’s disease-related peptide (Aβ42)? To answer such questions, we performed this work says Dr. Giri.

The findings of the research team have been recently published in the journal ‘Cell Reports Physical Science’. The paper has been co-authored by Dr. Rajanish Giri and his research scholars, Dr. Kundlik Gadhave and Ms. Taniya Bhardwaj, along with Prof. Michele Vendruscolo from the University of Cambridge, UK, and Prof. Vladimir Uversky from the University of South Florida, USA.

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