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

Altered Protein Shapes May Explain Differences in Some Brain Diseases

Published: Friday, July 05, 2013
Last Updated: Friday, July 05, 2013
Bookmark and Share
NIH-funded study finds that various strains of alpha-synuclein have diverse effects in neurons.

It only takes one bad apple to spoil the bunch, and the same may be true of certain proteins in the brain. Studies have suggested that just one rogue protein (in this case, a protein that is misfolded or shaped the wrong way) can act as a seed, leading to the misfolding of nearby proteins. According to an NIH-funded study, various forms of these seeds — originating from the same protein — may lead to different patterns of misfolding that result in neurological disorders with unique sets of symptoms.

“This study has important implications for Parkinson’s disease and other neurodegenerative disorders,” said National Institute of Neurological Disorders and Stroke (NINDS) Director Story Landis, Ph.D. “We know that among patients with Parkinson’s disease, there are variations in the way that the disorder affects the brains. This exciting new research provides a potential explanation for why those differences occur.”

An example of such a protein is alpha-synuclein, which can accumulate in brain cells, causing synucleinopathies, multiple system atrophy, Parkinson’s disease, Parkinson’s disease with dementia (PDD), and dementia with Lewy bodies (DLB). In addition, misfolded proteins other than alpha-synuclein sometimes aggregate, or accumulate, in the same brains. For example, tau protein collects into aggregates called tangles, which are the hallmark of Alzheimer’s disease and are often found in PDD and DLB brains. Findings from this study raise the possibility that different structural shapes, or strains, of alpha-synuclein may contribute to the co-occurrence of synuclein and tau accumulations in PDD or DLB.

In the new study, published in Cell, Jing L. Guo, Ph.D., and her colleagues from the University of Pennsylvania Perelman School of Medicine, Philadelphia, wanted to see if different preparations of synthetic alpha-synuclein fibrils would behave differently in neurons that were in a petri dish as well as in mouse brains. They discovered two strains of alpha-synuclein with distinct seeding activity in cultured neurons: while one strain (strain A) resulted in accumulation of alpha-synuclein alone, the other strain (strain B) resulted in accumulations of both alpha-synuclein and tau.

The researchers also injected strain A or strain B into the brains of mice engineered to make large amounts of human tau, and then monitored the formation of alpha-synuclein and tau aggregates at various time points. Mice that received injections of synuclein strain B showed more accumulation of tau — earlier and across more brain regions — compared to mice that received strain A.

The researchers also examined the brains of five patients who had PDD, some of whom also had Alzheimer’s. In this small sample, there was evidence of two different structural forms of alpha-synuclein, one in PDD brains and a distinctly different one in PDD/Alzheimer’s brains, supporting the existence of disease-specific strains of the protein in human diseases.

“We are just starting to do work with human tissues,” said Virginia M.Y. Lee, Ph.D., senior author of the study. “We are planning to look at the brains of patients who had Parkinson’s disease, PDD, or DLB to see if there are differences in the distribution of alpha-synuclein strains.”

Although the two strains used in this study were created in test tubes, the authors noted that in human brains, where the environment is much more complicated, the chances of forming additional disease-related alpha-synuclein strains may be greater.

“These different strains not only can convert normal alpha-synuclein into pathological alpha-synuclein within one cell, they also can morph into new strains as they pass from cell to cell, acquiring the ability to serve as a template to damage both normal alpha-synuclein and other proteins,” said Dr. Lee. “So certain strains, but not all strains, can act as templates to influence the development of other pathologies, such as tau tangles.”

She commented, “We are just beginning to understand some of these strains and there may be many others. We hope to find a way to identify strains that are relevant to human disease.”

This study was supported by grants from NINDS (NS53488) and the National Institute on Aging (AG17586). Additional funding was provided by the Marian S. Ware Alzheimer Program, Philadelphia, PA; the Dr. Arthur Peck Fund, Philadelphia, PA; The Jeff and Anne Keefer Fund, Philadelphia, PA; and the Parkinson Council, Bala Cynwyd, PA.

NINDS is the nation’s leading funder of research on the brain and nervous system. The NINDS mission is to reduce the burden of neurological disease — a burden borne by every age group, by every segment of society, by people all over the world.

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 3,500+ scientific posters on ePosters
  • More than 5,100+ 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 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

NIH Study Determines Key Differences between Allergic and Non-Allergic Dust Mite Proteins
Researchers at NIH have uncovered factors that lead to the development of dust mite allergy and assist in the design of better allergy therapies.
Thursday, October 20, 2016
Detecting Bacterial Infections in Newborns
Researchers tested an alternative way to diagnose bacterial infections in infants—by analyzing RNA biosignatures from a small blood sample.
Wednesday, September 14, 2016
$12.4M Awarded to Neural Regeneration Projects
The National Institutes of Health will fund six projects to identify biological factors that influence neural regeneration.
Friday, September 02, 2016
Oxygen Can Impair Cancer Immunotherapy
Researchers have identified a mechanism within the lungs where anticancer immune resposnse is inhibited.
Friday, August 26, 2016
New Inflammatory Disease Discovered
NIH researchers have discovered a rare and potentially deadly disease - otulipenia - the mostly affects children.
Tuesday, August 23, 2016
How Parkinson’s Disease Alters Brain Activity Over Time
The NIH study provides a new tool for testing experimental medications aimed at alleviating symptoms and slowing the rate at which the diseases damage the brain.
Tuesday, August 16, 2016
Genetic Cause of Rare Pediatric Neuropathy Identified
NIH mouse study identifies the mechanism responsible for a rare form of pediatric neuropathy.
Thursday, August 04, 2016
Uncovering Rhinovirus C Structure
Researchers have determined the structure of rhinovirus C. Their findings may aid the development of antiviral therapies and vaccines.
Wednesday, July 27, 2016
Advancing Protein Visualization
Cryo-EM methods can determine structures of small proteins bound to potential drug candidates.
Friday, May 27, 2016
Study Finds Factors That May Influence Influenza Vaccine Effectiveness
Researchers at NIH have suggested that the long-held approach to predicting seasonal influenza vaccine effectiveness may need to be revisited.
Wednesday, April 20, 2016
Visualizing a Cancer Drug Target at Atomic Resolution
Using cryo-electron microscopy, researchers were able to view, in atomic detail, the binding of a potential small molecule drug to a key protein in cancer cells.
Wednesday, February 10, 2016
Genomic Signature Shared by Five Types of Cancer
National Institutes of Health researchers have identified a striking signature in tumor DNA that occurs in five different types of cancer.
Monday, February 08, 2016
Natural Protein Points to New Inflammation Treatment
Findings may offer insight to effective treatments for inflammatory diseases, such as rheumatoid arthritis, psoriasis, and multiple sclerosis.
Friday, February 05, 2016
Biomarkers Outperform Symptoms in Parsing Psychosis Subgroups
Multiple biological pathways lead to similar symptoms - NIH-funded study.
Thursday, December 10, 2015
NIH Supports New Studies to Find Alzheimer’s Biomarkers in Down Syndrome
Initiative will track dementia onset, progress in Down syndrome volunteers.
Tuesday, December 01, 2015
Scientific News
Integrated Omics Analysis
Studying multi-omics promises to give a more holistic picture of the organism and its place in its ecosystem, however despite the complexities involved those within the field are optimistic.
Mass Spec Technology Drives Innovation Across the Biopharma Workflow
With greater resolving power, analytical speed, and accuracy, new mass spectrometry technology and techniques are infiltrating the biopharmaceuticals workflow.
NIH Study Determines Key Differences between Allergic and Non-Allergic Dust Mite Proteins
Researchers at NIH have uncovered factors that lead to the development of dust mite allergy and assist in the design of better allergy therapies.
Study Finds Key Regulator in Pulmonary Fibrosis
Researchers identify an enzyme that could open the way to therpies for chronic fatal lung disease.
Alzheimer’s-Linked Protein May Play Role in Schizophrenia
Researchers suggests a protein linked to cognitive decline in Alzheimer's also plays a role in genetic predisposition to schizophrenia.
Peptides vs. Superbugs
Scientists successfully develop a shuttle system made of liquid-crystalline nanomaterials that protect peptites.
Cocoa Compound Linked to Some Cardiovascular Biomarker Improvements
The study highlights the urgent need for large, long-term RCTs that improve understanding of how the short-term benefits of cocoa flavanol intake on cardiometabolic biomarkers may be translated into clinical outcomes.
Immune Approach Targets Humans Instead of Bacteria
Scientists show for the first time how bacterial superantigen toxins work, and how short peptides can block them and save lives.
Could 2D Mass Spec Breakthrough Lead to Medical Revolution?
Pharmaceutical research could be quicker and more precise, thanks to an innovative breakthrough in 2D mass spec from the University of Warwick.
Less is More in Ribosome Assembly
Research uncovers genetic "program" that allows for ribosome formation with a limited supply of magnesium.
Scroll Up
Scroll Down
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
3,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
5,100+ scientific videos