Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists identify 'clean-up' snafu that kills brain cells in Parkinson's disease

04.03.2013
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.

"We showed that when LRRK2 inhibits chaperone-mediated autophagy, alpha-synuclein doesn't get broken down and instead accumulates to toxic levels in nerve cells," said Dr. Cuervo.

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.

"We're now looking at ways to enhance the activity of this recycling system to see if we can prevent or delay neuronal death and disease," said Dr. Cuervo. "We've started to analyze some chemical compounds that look very promising."

Dr. Cuervo hopes that such treatments could help patients with familial as well as nonfamilial Parkinson's – the predominant form of the disease that also involves the buildup of alpha-synuclein.

Dr. Cuervo is credited with discovering chaperone-mediated autophagy. She has published extensively on autophagy and its role in numerous diseases, such as cancer and Huntington's disease , and its role in age-related conditions, including organ decline and weakened immunity. Dr. Cuervo is co-director of Einstein's Institute of Aging Research.

The paper is titled "Interplay of LRRK2 with chaperone-mediated autophagy." In addition to Dr. Cuervo, other Einstein contributors include Samantha J. Orenstein, a graduate student who performed most of this study as part of her Ph.D. thesis; Inmaculada Tasset, Ph.D.; Esperanza Arias, Ph.D.; and Hiroshi Koga, Ph.D., all members of Dr. Cuervo's group. Additional co-authors are: Sheng-Hang Kuo Ph.D., David Sulzer Ph.D., Etty Cortes, M.D., and Lawrence S. Honig, M.D. (Columbia University, NY); William Dauer, M.D., (University of Michigan, Ann Arbor, MI); Irene Fernandez-Carasa and Antonella Consiglio, Ph.D., (University of Barcelona, Barcelona Spain); and Angel Raya, M.D., Ph.D., (Institucio Catalana de Recerca I Estudies Avancas, Barcelona, Spain).

This work was supported by grants from the National Institute on Aging (AG031782 and AG08702), the National Institute of Neurological Disorders and Stroke Udall Center of Excellence both part of the National Institutes of Health; The Rainwaters Foundation, The Beatrice and Roy Backus Foundation, JPB Foundation; Parkinson's Disease Foundation; Fondazione Guido Berlucchi; Centers for Networked Biomedical Research; Ministry of Economy and Competitiveness; a Hirschl/Weill-Caulier Career Scientist Award; and a gift from Robert and Renee Belfer.

Albert Einstein College of Medicine

Albert Einstein College of Medicine of Yeshiva University is one of the nation's premier centers for research, medical education and clinical investigation. In 2012, Einstein received over $160 million in awards from the NIH for major research centers at Einstein in diabetes, cancer, liver disease, and AIDS, as well as other areas. Through its affiliation with Montefiore Medical Center, the University Hospital for Einstein, and six other hospital systems, the College of Medicine runs one of the largest residency and fellowship training programs in the medical and dental professions in the United States. For more information, please visit www.einstein.yu.edu and follow us on Twitter @EinsteinMed.

Kim Newman | EurekAlert!
Further information:
http://www.einstein.yu.edu

More articles from Health and Medicine:

nachricht Study suggests possible new target for treating and preventing Alzheimer's
02.12.2016 | Oregon Health & Science University

nachricht The first analysis of Ewing's sarcoma methyloma opens doors to new treatments
01.12.2016 | IDIBELL-Bellvitge Biomedical Research Institute

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>