New Delhi: Efforts to unravel the mystery around the highly debilitating disease of Alzheimer’s have got a shot in the arm with a recent study getting newer insight into the biomolecular mechanism for the formation of protein clusters/aggregates that are often seen in the disease.
Proteins are essential for virtually every process within the cell. But they can also pose problems if they undergo the process of aggregation and/or misfolding. There are more than 50 diseases that are associated with protein aggregation/misfolding.
Generally, when proteins get aggregated or misfolded, they deposit around the cells and kill them, leading to the onset of diseases.
In Alzheimer’s disease, studies have so far shown that it was linked with the deposition of misfolded peptides called amyloid β42 (Aβ42) in the spaces between nerve cells. Aβ42 is a peptide derived from a protein molecule called Amyloid Precursor Protein (APP).
The new study has taken this understanding to the next level. Signal peptides are short peptide units present at what is called the N-terminus of the proteins. They act as a postal address for the proteins inside the cell. Usually, as the protein reaches its destination, the signal peptides are cut off from the proteins and often degraded by the cellular machinery.
The new study has shown that these peptides can also combine with other peptides to form misfolded aggregates like Aβ42 and co-assemble with it.
Leader of the study and Associate Professor, School of Basic Sciences, Indian Institute of Technology (IIT) – Mandi, Dr. Rajanish Giri, noted that their study was the first report on an aggregation of signal peptides in isolation and said It would help in the future research that could provide the relation of other signal peptides to disease pathogenesis.
“In Amyloid precursor protein, so far only Aβ region was known to form toxic aggregates. Here, we discovered that the 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 study was conducted by an inter-institutional team. Besides Dr. Rajanish Giri, it consisted of his research scholars, Dr. Kundlik Gadhave and Ms. Taniya Bhardwaj, and Prof. Michele Vendruscolo from the University of Cambridge, UK, and Prof. Vladimir Uversky from the University of South Florida, USA. They have published a report on their findings in the journal ‘Cell Reports Physical Science’.
Courtesy: India Science Wire