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 3,300+ scientific posters on ePosters
  • More than 4,800+ 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
A Novel Cell Culture Model For Forensic Biology Experiments
Researchers have developed a new cell culture model which provides an efficient research tool in forensic biology.
Mapping Zika’s Routes to Developing Fetus
UC researchers show how Zika virus travels from a pregnant woman to her fetus, and also identified a drug that could stop it.
3D Printing Cartilage
3D bioprinting has successfully manufactured cartilage using bioink sourced from cow cartilage strands.
New Device can Study Electric Field Cancer Therapy
Microfluidic device allows study of electric field cancer therapy through low-intensity fields, preventing malignant cells spreading.
Scientists Culture Elusive Yellowstone Microbe
ORNL scientists have successfully isolated and cultured a Yellowstone sourced acidic hot-spring based microbe.
A 3D Paper-Based Microbial Fuel Cell
Researchers have developed a proof-of-concept 3D paper-based microbial fuel cell (MFC) that could take advantage of capillary action to guide the liquids through the MFC system and to eliminate the need for external power.
Just Gellin’: How To Grow Strong Muscles-On-A-Chip
USC researchers hope to usher in new treatments for patients with muscular dystrophy.
Lasers Carve the Path to Tissue Engineering
A new technique, developed at EPFL, combines microfluidics and lasers to guide cells in 3D space, overcoming major limitations to tissue engineering.
How Cancer Spreads in the Body
Cancer cells appear to depend on an unusual survival mechanism to spread around the body, according to an early study led by Queen Mary University of London.
Tumor Cells Develop Predictable Characteristics
Scientists have discovered that cancer cells at the edge of a tumor that are close to the surrounding environment are predictably different from the cells within the interior of the tumor.
Skyscraper Banner

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
3,300+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,800+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!