Corporate Banner
Satellite Banner
Cell Culture
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Protein Build-up Leads to Neurons Misfiring

Published: Friday, July 20, 2012
Last Updated: Friday, July 20, 2012
Bookmark and Share
New evidence shows that alpha-synuclein protein build-up inside neurons causes them to not only become "leaky," but also to misfire due to calcium fluxes.

The findings — the first recorded in vivo using a transgenic mouse model of Parkinson's disease — are published in today's (July 18) issue of the Journal of Neuroscience and provide new insights into how Parkinson's disease and other neurodegenerative disorders known as synucleinopathies work and progress at the cellular level.

Previous in vitro studies using cell cultures had suggested abnormal accumulation of alpha-synuclein dysregulated intracellular handling and movement of calcium, which is used as a signaling molecule and neurotransmitter. It was unclear, however, whether calcium alterations occurred in more complex, living animals.

"This is the first time we've been able to verify the role of alpha-synuclein aggregates in vivo," said senior author Eliezer Masliah, M.D., professor of neurosciences and pathology.

"The aggregates affect the cell membrane of neurons, making them more porous. They also affect the membranes of organelles inside neurons, such as the mitochondria that are part of the cell's machinery for generating energy. Energy is necessary to pump calcium in and out of the cell. If mitochondria membranes are compromised, calcium accumulates, further damaging the neuron and causing it to misfire."

Masliah said the new revelations, made using imaging technologies developed by first author Anna Devor, Ph.D., associate adjunct professor of neuroscience, may help scientists and doctors quantify and repair neuronal damage caused by alpha-synuclein accumulation.

"We have already started to utilize this discovery as a bio-marker and reporter of neuronal damage," said Masliah. "We have compounds developed in collaboration with others to ‘plug' the holes in the neurons and mitochondria and prevent the abnormal calcium currents. We can monitor in real-time in live animals how our drugs revert the toxic effects of alpha-synuclein. This represents a unique and fast strategy to evaluate novel compounds."

Co-authors are Lidia Reznichenko, Qun Cheng, Krystal Nizar, Payam A. Saisan, Edward M. Rockenstein, Tanya Gonzalez, Christina Patrick, Brian Spencer and Paula Desplats, Department of Neurosciences, UC San Diego; Sergey L. Gratiy, Department of Radiology, UC San Diego; Anders M. Dale, departments of Neurosciences and Radiology, UC San Diego; Anna Devor, departments of Neurosciences and Radiology, UC San Diego; and Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School.

Funding for this research came, in part, from the National Institute on Aging (grant AG-02270), The National Institute of Neurological Disorders and Stroke (grants NS-051188, NS-057198 and NS-0507096), the National Institute of Biomedical Imaging and Bioengineering (grants EB-009118 and EB-000790) and the Short Family Fund.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,000+ scientific posters on ePosters
  • More than 4,500+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Cellular “ORACLs” to Aid Drug Discovery
New approach for finding therapeutics is inspired by face-recognition software.
Wednesday, December 16, 2015
Artificial Kidney Research Gets A Boost
Development of a surgically implantable, artificial kidney — a promising alternative to kidney transplantation or dialysis for people with end-stage kidney disease — has received a $6 million boost.
Monday, November 09, 2015
Growing Spinal Disc Tissue
Scientists develop new method for growing spinal disc tissue in the lab for combating chronic back pain.
Friday, July 03, 2015
May the Cellular Force be With You
Like tiny construction workers, cells sculpt embryonic tissues and organs in 3D space.
Friday, December 13, 2013
Understanding a Protein’s Role in Familial Alzheimer’s
Researchers have used genetic engineering of human iPSC’s to specifically and precisely parse the roles of a key mutated protein in causing familial Alzheimer's disease (AD).
Monday, November 18, 2013
Developmental Protein Plays Role in Spread of Cancer
A protein used by embryo cells during early development, and recently found in many different types of cancer, apparently serves as a switch regulating metastasis.
Tuesday, June 18, 2013
Nobel Prize Winner Yamanaka Remains at Forefront of Fast-Moving Stem Cell Field
Shinya Yamanaka, MD, PhD, named winner of the 2012 Nobel Prize for Physiology or Medicine, said he was doing some housecleaning when the call came in, and was “very surprised.”
Friday, October 12, 2012
Well-known Protein Reveals New Tricks
A protein called "clathrin," which is found in every human cell and plays a critical role in transporting materials within them, also plays a key role in cell division.
Friday, September 07, 2012
Scientific News
'Kidney on a Chip' Facilitates Safer Drug Dosing
University of Michigan researchers have used a "kidney on a chip" device to mimic the flow of medication through human kidneys and measure its effect on kidney cells.
New Method Allows First Look At Embryo Implantation
Researchers at The Rockefeller University develop a method that shows the molecular and cellular processes that occur up to day 14 after fertilization.
Detecting Nano Amounts In Environmental Samples
The NanoUmwelt project is developing a technique that can detect nanomaterials in a variety of environmental samples.
Shape Of Tumor May Affect Whether Cells Can Metastasize
Illinois researchers found that the shape of a tumor may play a role in how cancer cells become primed to spread.
‘Mini-Brains’ to Study Zika
Novel tool expected to speed research on brain and drug development.
Cytokine Triggers Immune Response at Expense of Blood Renewal
Research highlights promise of Anti-IL-1 drugs to treat chronic inflammatory disease.
Micro Heart Muscle Created from Stem Cells
Researchers have designed a new way to create micro heart muscle from stem cells using a unique dog bone dish.
“Secret Sauce” for Personalized, Functional Insulin-producing Cells
Researchers uncover molecular switch to make effective sugar-responsive, insulin-releasing cells in a dish, offering hope for diabetes therapy.
Insights into Early Human Embryo Development
Researchers at Karolinska Institutet and the Ludwig Cancer Research in Stockholm have conducted a detailed molecular analysis of the embryo’s first week of development.
Boosting Gene Transfer Capabilities
A new and highly efficient method for gene transfer has been developed.
SELECTBIO

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,000+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,500+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!