Mandi 22 Nov : .Researchers from the Indian Institute of Technology Mandi discovered a biomolecular mechanism that allows the formation of proteins clusters and aggregates, which are common in Alzheimer’s. Alzheimer’s disease is the most prevalent form of dementia.It slowly damages memory and other vital mental functions.
Researchers from University of South Florida, USA, as well as University of Cambridge in UK and UK showed that the signal peptide of Amyloid Precursor protein (APP) could be combined with other peptides, forming misfolded aggregates such that Amyloid beta peptide can deposit outside of cells, causing diseases.
The cell’s signal peptides serve as an address to the proteins.
Although proteins are vital for almost every cell process, they can have harmful consequences if their functions are disrupted by aggregation or misfolding.There are more than 50 diseases that are associated with protein aggregation/misfolding.
Amyloid beta peptide, a misfolded protein, can be found in spaces between nerve cells and is associated with Alzheimer’s.
It was not known if signal peptides of APP could also form disease-causing aggregates.
Amyloid precursor protein has so far been known to create toxic aggregates in the Ass region.We found that the Signal peptide from Amyloid precursor protein forms toxic aggregates and also increases the aggregation Amyloid beta-peptide peptide under in vitro conditions,” stated Dr.Rajanish Giri (Associate Professor at IIT-Mandi School of Basic Sciences).
Giri observed in the Cell Reports Physical Science study that signal peptides often get cut as proteins reach their destination.
This is commonly seen by the cell machinery.
The team looked at the aggregation patterns of a signal peptide from the APP to understand why it was cut off.This is now called APP1-17SP.
The researchers found that APP1-17SP is associated with Alzheimer’s-associated peptide Amyloid beta peptide, and creates aggregates of higher toxicity.
The team conducted experiments using dye-based assays on the APP1-17SP and discovered that it can bind with these aggregate-tracking colors.The formation of fibrillar aggregates was also possible in similar experiments using APP1-17SP and Amyloid beta peptide peptide.
The Amyloid beta peptide-APP1-17SP combination had a higher cytotoxicity than Amyloid beta peptide or APP1-17SP individually.
Giri stated, “This is the first study on an isolation of signal peptide aggregation.” Our study suggests a link between signal-peptide aggregate and Alzheimer’s amloid beta peptide protein aggregation.
He noted that “this study will aid in future research which could provide relationship of other signal proteins to disease pathogenesis.”
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