Researchers at the University of Texas (UT) Southwestern Medical Center, reporting in the July 6, 2018 issue of the Journal of Biological Chemistry, have uncovered details of how cells take in corrupted proteins that can turn normal proteins corrupt, leading to neurodegenerative diseases such as Alzheimer's and Parkinson's. The new article is titled “Specific Glycosaminoglycan Chain Length and Sulfation Patterns Are Required for Cell Uptake of Tau Versus Α-Synuclein and -Amyloid Aggregates.” Understanding the molecular details of how these proteins spread from cell to cell could lead to therapies to halt disease progression. Alzheimer's and Parkinson's are associated with particular proteins in the brain misfolding, aggregating, and inducing normal proteins to misfold and aggregate. Dr. Marc Diamond's group at UT Southwestern discovered in 2013 that to enter new cells and propagate misfolding, the disease-associated proteins tau, alpha-synuclein, and amyloid-beta must bind to a type of sugar-protein molecule called heparan sulfate proteoglycan (HSPG) on the cell's surface. This binding triggers the cell to bring the corrupted protein inside. In the new study, the group sought to understand more about how this process worked. "The question was, how specific is this (process)? Or is it not specific at all?" asked Dr. Barbara Stopschinski, the physician and researcher in Dr. Diamond's lab who oversaw the new work. What were the details of the chemical communication between HSPG and tau that triggered tau's entry into the cells? And was this process different for alpha-synuclein (associated with Parkinson's disease), amyloid-beta, and tau (both associated with Alzheimer's disease)?
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