Researchers at the Indian Institute of Technology (IIT) Mandi have discovered an important biomolecular mechanism for the formation of protein clusters and aggregates that are often seen in Alzheimer’s disease.
An inter-institutional team comprising researchers from the IIT Mandi, University of Cambridge, UK, and the University of South Florida, USA, studied the aggregation pattern of a signal peptide of the APP protein.
The findings of the research team have been recently published in the journal “Cell Reports Physical Science”.
The researchers have shown that signal peptide of the amyloid precursor protein (APP) can co-aggregate with Amyloid beta peptide (A42). This A42, known for the pathogenesis of Alzheimer’s disease, a most common form of dementia that slowly destroys memory and other important mental functions.
According to the team, while proteins are essential for virtually every process within the cell, their disturbed functions due to aggregation or misfolding can result in harmful effects.
Syed Mushtaq Ali Trophy: defending champions Tamil Nadu thrash Hyderabad by 8 Wickets, storm into Final
There are more than 50 diseases that are associated with protein aggregation and 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).
“In Amyloid precursor protein, so far only A 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 A42 peptide, under in-vitro conditions,” said Rajanish Giri, associate professor, School of Basic Sciences, IIT Mandi.
Signal peptides are short peptide units present at the N-terminus of the proteins, which play a role in protein targeting. They act as a postal address for the proteins inside the cell. Usually, as the protein reaches to its destination, the signal peptides are cut off from the proteins and often degraded by the cellular machinery.
“Can they affect other cellular processes? It is possible that they could combine with other peptides to form mis-folded aggregates like A42 that deposit outside of cells and cause diseases,” he said.
Giri said this study will help in future research that could provide relation of other signal peptides to disease pathogenesis.