IIT Mandi discovers mechanism for formation of protein clusters in Alzheimer’s

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.  

Researchers at the Indian Institute of Technology (IIT) Mandi have discovered an important biomolecular mechanism for the formation of protein clusters/aggregates that are often seen in Alzheimer’s disease. Alzheimer’s is the most common cause of dementia -- a continuous decline in thinking, behavioural and social skills that affects a person’s ability to function independently.  

The team, which was led by Rajanish Giri, School of Basic Sciences, IIT Mandi, also included researchers from the University of Cambridge, the UK, and University of South Florida in the US. It has has shown that signal peptides of the amyloid precursor protein (APP) can co-aggregate with amyloid beta-peptide (A42). Signal peptides act as a postal address for the proteins inside the cell. 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 42 (A42) in the spaces between nerve cells. A42 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 kill them, leading to many diseases. So far, it was not known whether signal peptides 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 (A42)? To answer this, we performed this work, said Rajanish Giri from IIT Mandi. 

The findings of the research team have recently been published in the journal, ‘Cell Reports Physical Science’. 

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