Unraveling the origin of Alzheimer's disease: Researchers find new hints that could explain how the disease spreads in human brains
Case Western Reserve University researchers studying prions — misfolded proteins that cause lethal incurable diseases — have identified for the first time surface features of human prions responsible for their replication in the brain.
The ultimate goal of the research is to help design a strategy to stop prion disease in humans — and, ultimately, to translate new approaches to work on Alzheimer’s and other neurodegenerative diseases.
Scientists have yet to discover the exact cause of Alzheimer’s disease, but largely agree that protein issues play a role in its emergence and progression. Alzheimer’s disease afflicts more than 6 million people in the U.S., and the Alzheimer’s Association estimates that their care will cost an estimated $355 billion this year.
Research was done at the Safar Laboratory in the Department of Pathology and the Center for Proteomics and Bioinformatics at Case Western Reserve University School of Medicine, and at Case Western Reserve’s Center for Synchrotron Bioscience at Brookhaven Laboratories in New York. Jiri Safar, professor of pathology, neurology and neurosciences at the Case Western Reserve School of Medicine, leads the work. The report, “Structurally distinct external domains drive replication of major human prions,” was published in the June 17 issue of PLOS Pathogens.
Prions were first discovered in the late 1980s as a protein-containing biological agent that could replicate itself in living cells without nucleic acid. The public health impact of medically transmitted human prion diseases — and also animal transmissions of bovine spongiform encephalopathy (BSE, “mad cow disease”) prions — dramatically accelerated the development of a new scientific concept of self-replicating protein.
Human prions can bind to neighboring normal proteins in the brain, and cause microscopic holes. In essence, they turn brains into sponge-like structures and lead to dementia and death. These discoveries led to the ongoing scientific debate on whether prion-like mechanisms may be involved in the origin and spread of other neurodegenerative disorders in humans.
