Scientists Identify 'Clean-Up' Snafu That Kills Brain Cells In Parkinson's Disease
BRONX, N.Y., March 3, 2013 /PRNewswire-USNewswire/ -- Researchers at Albert Einstein College of Medicine of Yeshiva University have discovered how the most common genetic mutations in familial Parkinson's disease damage brain cells. The study, which published online today in the journal Nature Neuroscience, could also open up treatment possibilities for both familial Parkinson's and the more common form of Parkinson's that is not inherited.
Parkinson's disease is a gradually progressing disorder of the nervous system that causes stiffness or slowing of movement. According to the Parkinson's Disease Foundation, as many as one million Americans are living with the disease.
The most common mutations responsible for the familial form of Parkinson's disease affect a gene called leucine-rich repeat kinase-2 ( LRRK2). The mutations cause the LRRK2 gene to code for abnormal versions of the LRRK2 protein. But it hasn't been clear how LRRK2 mutations lead to the defining microscopic sign of Parkinson's: the formation of abnormal protein aggregates inside dopamine-producing nerve cells of the brain."Our study found that abnormal forms of LRRK2 protein disrupt an important garbage-disposal process in cells that normally digests and recycles unwanted proteins including one called alpha-synuclein – the main component of those protein aggregates that gunk up nerve cells in Parkinson's patients," said study leader Ana Maria Cuervo, M.D., Ph.D., professor of developmental and molecular biology, of anatomy and structural biology, and of medicine and the Robert and Renee Belfer Chair for the Study of Neurodegenerative Diseases at Einstein. The name for the disrupted disposal process is chaperone-mediated autophagy (the word "autophagy" literally means "self-eating"). It involves specialized molecules that "guide" old and damaged proteins to enzyme-filled structures called lysosomes; there the proteins are digested into amino acids, which are then recycled within the cell.
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