Navigation Links
Improper protein digestion in neurons identified as a cause of familial Parkinson's
Date:3/5/2013

NEW YORK, NY (March 5, 2013) Researchers at Columbia University Medical Center (CUMC), with collaborators at the 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 mutations block an intracellular system that normally prevents a protein called alpha-synuclein from reaching toxic levels in dopamine-producing neurons. The findings suggest that interventions aimed at enhancing this digestive system, or preventing its disruption, may prove valuable in the prevention or treatment of Parkinson's. The study was published March 3 in the online edition of the journal Nature Neuroscience.

Parkinson's disease is characterized by the formation of Lewy bodies (which are largely composed of alpha-synuclein) in dopamine neurons. In 1997, scientists discovered that a mutation in alpha-synuclein can lead to Lewy body formation. "But alpha-synuclein mutations occur in only a tiny percentage of Parkinson's patients," said co-lead author David L. Sulzer, PhD, professor of neurology, pharmacology, and psychiatry at CUMC. "This meant that there must be something else that interfered with alpha-synuclein in people with Parkinson's."

Dr. Sulzer and his colleagues suspected that a gene called leucine-rich repeat kinase-2 (LRRK2) might be involved. LRRK2 mutations are the most common mutations to have been linked to Parkinson's. The current study aimed to determine how these mutations might lead to the accumulation of alpha-synuclein.

"We found that abnormal forms of LRRK2 protein disrupt a critical protein-degradation process in cells called chaperone-mediated autophagy," said Dr. Sulzer. "One of the proteins affected by this disruption is alpha-synuclein. As this protein starts to accumulate, it becomes toxic to neurons." Delving deeper, the researchers found that LRRK2 mutations interfere with LAMP-2A, a lysosome membrane receptor that plays a key role in lysosome function.

(Chaperone-mediated autophagy, or CMA, is responsible for transporting old or damaged proteins from the cell body to the lysosomes, where they are digested into amino acids and then recycled. In 2004, Dr. Sulzer and the current paper's other co-lead author, Ana Maria Cuervo, MD, PhD, professor of developmental & molecular biology, of anatomy & structural biology, and of medicine at Albert Einstein College of Medicine of Yeshiva University, showed that alpha-synuclein is degraded by the CMA pathway.)

"Now that we know this step that may be causing the disease in many patients, we can begin to develop drug treatments or genetic treatments that can enhance the digestion of these disease-triggering proteins, alpha-synuclein and LRRK2, or that remove alpha-synuclein," said Dr. Sulzer.

While LRRK2 mutations are the most common genetic cause of Parkinson's, it is too early to tell whether these findings, and therapies that might stem from them, would apply to patients with non-familial Parkinson's, the more common form of the disease. "Right now, all we can say is that it looks as though we've found a fundamental pathway that causes the buildup of alpha-synuclein in people with LRRK2 mutations and links these mutations to a common cause of the disease. We suspect that this pathway may be involved in many other Parkinson's patients," said Dr. Sulzer.

The study involved mouse neurons in tissue culture from four different animal models, neurons from the brains of patients with Parkinson's with LRRK2 mutations, and neurons derived from the skin cells of Parkinson's patients via induced pluripotent stem (iPS) cell technology. All the lines of research confirmed the researchers' discovery.


'/>"/>

Contact: Karin Eskenazi
ket2116@columbia.edu
212-342-0508
Columbia University Medical Center
Source:Eurekalert

Related medicine news :

1. Hope in stopping melanoma from spreading: Inhibiting protein prevents metastasis to lungs in mice
2. Selexis SA Announces Publication in Metabolic Engineering of Data Demonstrating Improvement of Therapeutic Protein Secretion with Engineered CHO Cells
3. Protein synthesis blocker may hold key to reducing effects of traumatic events
4. Discovery of executioner protein opens door to new options for stroke ALS, spinal cord injury
5. Researchers discover how to shutdown cancers powerful master protein
6. Protein balance key in preventing cancer
7. Resurrection of 3-billion-year-old antibiotic-resistance proteins
8. Researchers at the UH Cancer Center discover protein that may control the spread of cancer
9. Cell scaffolding protein fascin-1 is hijacked by cancer
10. BioTrust Low Carb Protein Review Revealed By BioTrust Nutrition Reviews
11. Data on novel IL-1 inhibitor protein for topical treatment of dry eye disease published
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... (PRWEB) , ... October 13, 2017 , ... PurhealthRX ... CBD Oil utilizing Purzorb™ technology. Applying the Purzorb™process to full spectrum CBD oil will ... and providing a CBD form that can be easily incorporated into liquid products, while ...
(Date:10/13/2017)... (PRWEB) , ... October 13, 2017 , ... Many families ... However, many long-term care insurance companies have a waiver for care if the client ... elimination period, when the family pays for care, is often waived, so the benefits ...
(Date:10/13/2017)... , ... October 13, 2017 , ... Yisrayl Hawkins, Pastor ... that explains one of the most popular and least understood books in the Holy ... and puzzling descriptions that have baffled scholars for centuries. Many have tossed it off ...
(Date:10/13/2017)... ... ... “America On The Brink”: the Christian history of the United States and the loss ... author, William Nowers. Captain Nowers and his wife, Millie, have six children, ten ... the Navy. Following his career as a naval aviator and carrier pilot, he ...
(Date:10/12/2017)... ... October 12, 2017 , ... The company has developed ... consumer and regulatory authorities worldwide. From Children’s to Adults 50+, every formula has ... highest standard. , These products are also: Gluten Free, Non-GMO, Vegan, Soy ...
Breaking Medicine News(10 mins):
(Date:9/28/2017)... Hill-Rom Holdings, Inc. (NYSE: HRC), will host ... webcast on Friday, November 3, 2017, beginning at 7:00 ... approximately 8:30 a.m. (CDT) / 9:30 a.m. (EDT). ... performance and guidance for 2018, Hill-Rom executives will also ... performance, and long-range financial outlook through 2020. ...
(Date:9/25/2017)... --  Montrium , an industry leader in powerful ... Trial Master Files & Inspection Readiness Conference ( ... Services has selected eTMF Connect to ... a leading European contract research organization (CRO), will ... enable greater collaboration with sponsors, improve compliance and ...
(Date:9/22/2017)... -- AVACEN Medical (AVACEN) announced that its CE-Marked AVACEN ... with the widespread pain associated with fibromyalgia in the ... Essex, England commented, "I had difficulty ... sleep at all, tremendous pain, with every movement sending ... AVACEN 100] enough, how this has and is helping ...
Breaking Medicine Technology: