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

Public release date: 2-Jan-2008
http://www.eurekalert.org/pub_releas...-erd122107.php

(BRONX, NY) -- 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.


Other Einstein scientists involved in the research were lead author Marta Martinez-Vicente, Susmita Kaushik, Ashish Massey and Dr. Antonia Follenzi. This work also included collaborators from Columbia University, the University of Pennsylvania, and Harvard Medical School.

My understanding of the paper is the following: My knowledge of biology is next to null so I will welcome comments and corrections
The cell has an elaborate “sewage” system (autophagy) which rids itself from faulty molecules (faulty enzymes? Which are called mutants such as the famous alpha-synuclein which act as poisons). BUT the ‘famous’ dopamine joins with some of these faulty molecules making a “sticky” kind of compound which renders the sewage system ineffective (like closing the sewers!) . Now with closed sewers, the poisons accumulate in the cell causing its death.
It is amazing that the main culprit is DOPAMINE ! . IT IS OUR SAVER AND OUR KILLER !
Such is the irony of life

You keep saying you aren't good in biology, but sound pretty educated to me.

Vicky

The truth is that my knowledge in Biology does not go much beyond school classes about 46 years back ... but I am trying hard to catch up . I am an electrical engineer !!

http://www.kptm.com/Global/story.asp...&nav=menu606_2

Posted: Jan 10, 2008 06:11 AM

Parkinson's Disease Breakthrough

UNMC researchers hope they're one step closer to a vaccine to treat an incurable and debilitating disease. Local research some say provides a breakthrough in treating patients with Parkinson's disease.

Monnie Lindsay can barely lift a glass to her mouth without shaking. "For us, living with Parkinson's is a horrible disease that continues to progress," says Lindsay.

Monnie was diagnosed with Parkinson's 14 years ago. She says her right arm stopped moving when she was only 38 years old. "It's like living life in a locked box, locked inside our own body."

UNMC researchers now say they may have unlocked the secret to creating a vaccine. "That can be used to treat the disease and alleviate much of the suffering and debilitations that people incur," says one of the lead researchers, Dr. Howard Gendelman.

Dr.Gendelman says certain proteins build up in the brain, clogging like a drain. He says the brain cannot get rid of the clogs and in large amounts, the proteins damage the nerve cells. "If we believe we can harness the immune system and attack these aggregates, we can break them down and allow the brain and the natural immune system to clear them and get at the root cause of Parkinson's disease," says Dr. Gendelman.

It's exciting news for patients like Monnie. "It's a huge development and huge breakthrough, so I'm hoping that we can continue to work with Dr. Gendelman and his team and that we can bring some exciting research to Nebraska," says Lindsay.

A breakthrough researchers hope will lead to a vaccine.

It could still be years before the FDA approves a vaccine for Parkinson's disease. But, researchers say their recent findings will serve as a cornerstone for other scientists to look for new treatments.