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 appears in The Journal of Clinical Investigation and 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.
- PHYSICAL SCIENCES
- EARTH SCIENCES
- LIFE SCIENCES
- SOCIAL SCIENCES
Subscribe to the newsletter
Stay in touch with the scientific world!
Know Science And Want To Write?
- Radical Rethink: Sugars Are The Only Cause Of Tooth Decay
- Life After The 125 GeV Higgs: What Is Left Of Two-Higgs Doublet Models
- Being Too Analytical Could Push Ethics Out The Door
- It's Almost 2015 - So Where Is My Hoverboard?
- Rapidly Evolving Lizards Show How Some Creatures Can Adapt To Beat Climate Change
- Drugs For Mild Hypertension In Low Risk People Questioned
- Keytruda: FDA Approves Melanoma Drug That Uses Immune System To Fight Cancer
- "Hi Luis,thanks for the quote. Of course we are looking in every corner of phase space... Cheers,T...."
- "Hello Tony,of course ATLAS and CMS are looking for new Higgs states in that mass region and..."
- "Dear Inventor,it is not a generalization, it is the necessary result of the introduction of the..."
- "I doubt she read it far enough to see the details of the proposal. You are welcome to recommend..."
- "I do hope Hontas actually read your proposal (bet) before deleting it, since I truly hope she takes..."
- Imaging identifies asymptomatic people at risk for stroke
- Researchers debunk myth about Parkinson's disease
- Dental and nutrition experts call for radical rethink on free sugars intake
- Study shows consumption of high-fat dairy products is associated with a lower risk of developing diabetes
- Study adds to cancer-fighting promise of combined immunotherapy-radiation treatment