Einstein researchers discover important clue to the cause of Parkinson's disease

Jan 02, 2008

A glitch in the mechanism by which cells recycle damaged components may trigger Parkinson’s disease, according to a study by scientists at the Albert Einstein College of Medicine of Yeshiva University. The research, which appears in the January 2 advance online issue of The Journal of Clinical Investigation, could lead to new strategies for treating Parkinson’s and other neurodegenerative diseases.

All cells depend on a surveillance system known as autophagy (which literally means “self eating”) to digest and recycle the damaged molecules that arise as cells age. In autophagy, defective proteins and other molecules are transported to membrane-bound sacs called lysosomes. After attaching to the lysosomal membrane, the molecules enter the lysosome, where they are digested by enzymes. This cleanup process may be particularly important for nerve cells, which generate defective molecules more rapidly than most other types of cells. When autophagy is impaired, toxic compounds can accumulate and cause cell death.

“It is widely suspected that accumulation of a particular protein, known as alpha-synuclein, within affected nerve cells of Parkinson’s disease patients contributes to the death of these cells,” says Dr. Ana Maria Cuervo, senior author of the article and associate professor of anatomy & structural biology at Einstein.

Dr. Cuervo previously showed that mutant forms of alpha-synuclein—found in the five to 10 percent of patients who have familial Parkinson’s disease—are poorly digested via autophagy and also block the breakdown of other substances. While these alpha-synuclein mutations are rare, other modifications of alpha-synuclein—phosphorylated and oxidized forms, for example—can be found in the brains of all Parkinson’s disease patients.

In this study, Dr. Cuervo and her colleagues looked at how several different modified forms of alpha-synuclein affected autophagy in vitro and in tissue culture. One particular modification of alpha-synuclein was found to interfere with autophagy: the compound created by the interaction of alpha-synuclein with dopamine, the main neurotransmitter produced by the nerve cells damaged in Parkinson’s disease.

“Alpha-synuclein molecules modified by dopamine bound tightly to the lysosomal membrane, but they got stuck there and weren’t effectively transported into the lysosome,” says Dr. Cuervo. As a result, the alpha-synuclein molecules altered by dopamine were poorly degraded, and the presence of these molecules on the lysosomal membranes interfered with autophagic digestion of other compounds as well.

“We propose that inhibition of autophagy caused by dopamine’s alteration of alpha-synuclein could explain the selective death of dopamine-producing nerve cells in Parkinson’s disease,” says Dr. Cuervo, who notes that interference with autophagy has also been implicated in other neurodegenerative diseases including Alzheimer’s.

“By devising strategies for boosting autophagy in nerve cells or suppressing the chemical reactions that interfere with the autophagy—by lowering alpha synuclein expression, for example--we may be able to treat patients afflicted with these conditions,” she says.


Source: Albert Einstein College of Medicine

Explore further: Vietnam battles fatal measles outbreak

add to favorites email to friend print save as pdf

Related Stories

Human cells build protein cages to trap invading Shigella

Dec 04, 2011

In research on the never-ending war between pathogen and host, scientists at the Pasteur Institute in Paris have discovered a novel defensive weapon, a cytoskeletal protein called septin, that humans cells deploy to cage ...

Recommended for you

US orders farms to report pig virus infections

11 hours ago

The U.S. government is starting a new program to help monitor and possibly control the spread of a virus that has killed millions of pigs since showing up in the country last year.

Foreigner dies of MERS in Saudi

11 hours ago

A foreigner has died after she contracted MERS in the Saudi capital, the health ministry said on announced Friday, bringing the nationwide death toll to 73.

Vietnam battles fatal measles outbreak

15 hours ago

Vietnam is scrambling to contain a deadly outbreak of measles that has killed more than 100 people, mostly young children, and infected thousands more this year, the government said Friday.

New clues on tissue scarring in scleroderma

16 hours ago

A discovery by Northwestern Medicine scientists could lead to potential new treatments for breaking the cycle of tissue scarring in people with scleroderma.

User comments : 0

More news stories

Treating depression in Parkinson's patients

A group of scientists from the University of Kentucky College of Medicine and the Sanders-Brown Center on Aging has found interesting new information in a study on depression and neuropsychological function in Parkinson's ...

Impact glass stores biodata for millions of years

(Phys.org) —Bits of plant life encapsulated in molten glass by asteroid and comet impacts millions of years ago give geologists information about climate and life forms on the ancient Earth. Scientists ...