We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
PURITAN MEDICAL

Download Mobile App




Researchers Define the Structure of Parkinson's Disease Protein Aggregates

By LabMedica International staff writers
Posted on 12 Apr 2016
Print article
The use of advanced imaging techniques has enabled biochemists to determine the molecular structure of alpha-synuclein protein fibrils such as those found in the brains of individuals with Parkinson's disease.

The accumulation of misfolded alpha-synuclein amyloid fibrils leads to the formation of insoluble aggregates that have been implicated in several neurodegenerative diseases, including Parkinson's disease, dementia with Lewy bodies, and Alzheimer's disease. It has been exceedingly difficult to define the structure of alpha-synuclein fibrils due to their insolubility and complexity.

Investigators at the University of Illinois (Champaign-Urbana, USA) and their collaborators used advanced imaging techniques such as magic-angle spinning nuclear magnetic resonance (a type of solid state NMR) to measure the placement of atoms in samples of alpha-synuclein.

They described in the March 28, 2016, online edition of the journal Nature Structural and Molecular Biology a structure with common amyloid features including parallel, in-register beta-sheets and hydrophobic-core residues. The structure revealed substantial complexity arising from diverse structural features including an intermolecular salt bridge, a glutamine ladder, close backbone interactions involving small residues, and several steric zippers stabilizing a new orthogonal Greek-key topology. The results were validated using EM (electron microscope) and X-ray fiber diffraction.

The investigators synthesized alpha-synuclein fibrils according to their structural data and showed that these fibrils induced robust Parkinson's-like pathology in primary neuronal cultures.

"We had to find patterns in the data and systematically test all the possibilities for how the protein would fit together," said senior author Dr. Chad Rienstra, professor of chemistry at the University of Illinois. "It is like when you solve a really complex puzzle, you know you have it right at the end because all the pieces fit together. That is what we got with this structure. This is the first structure of the full-length fibril protein, which is now well established to be important for the pathology of Parkinson's disease. Knowing that structure will open up many new areas of investigation for diagnosing and treating Parkinson's disease."

"We think that the structure that we resolved of alpha-synuclein fibrils will be really significant in the immediate future and has use for diagnosing Parkinson's in patients before they are symptomatic," said Dr. Rienstra. "Once people start having symptoms, whether of Alzheimer's or Parkinson's, in many ways it is a little too late to be effective with therapy. But if you catch it early, I think there is a lot of promise for therapies that are being developed. Those are all relying upon the structures that we are solving."

Related Links:

University of Illinois


Platinum Member
COVID-19 Rapid Test
OSOM COVID-19 Antigen Rapid Test
Magnetic Bead Separation Modules
MAG and HEATMAG
Complement 3 (C3) Test
GPP-100 C3 Kit
New
Gold Member
Magnetic Bead Separation Modules
MAG and HEATMAG

Print article

Channels

Clinical Chemistry

view channel
Image: The 3D printed miniature ionizer is a key component of a mass spectrometer (Photo courtesy of MIT)

3D Printed Point-Of-Care Mass Spectrometer Outperforms State-Of-The-Art Models

Mass spectrometry is a precise technique for identifying the chemical components of a sample and has significant potential for monitoring chronic illness health states, such as measuring hormone levels... Read more

Molecular Diagnostics

view channel
Image: AI analysis of DNA fragmentomes and protein biomarkers noninvasively detects ovarian cancer (Photo courtesy of Adobe Stock)

Blood-Based Machine Learning Assay Noninvasively Detects Ovarian Cancer

Ovarian cancer is one of the most common causes of cancer deaths among women and has a five-year survival rate of around 50%. The disease is particularly lethal because it often doesn't cause symptoms... Read more

Hematology

view channel
Image: The CAPILLARYS 3 DBS devices have received U.S. FDA 510(k) clearance (Photo courtesy of Sebia)

Next Generation Instrument Screens for Hemoglobin Disorders in Newborns

Hemoglobinopathies, the most widespread inherited conditions globally, affect about 7% of the population as carriers, with 2.7% of newborns being born with these conditions. The spectrum of clinical manifestations... Read more

Immunology

view channel
Image: The groundbreaking treatment approach has shown promise in hard-to-treat cancers (Photo courtesy of 123RF)

Genetic Testing Combined With Personalized Drug Screening On Tumor Samples to Revolutionize Cancer Treatment

Cancer treatment typically adheres to a standard of care—established, statistically validated regimens that are effective for the majority of patients. However, the disease’s inherent variability means... Read more

Pathology

view channel
Image: ‘Virtual biopsy’ allows clinicians to analyze skin noninvasively (Photo courtesy of Stanford Medicine)

Virtual Skin Biopsy Determines Presence of Cancerous Cells

When dermatologists spot an unusual mark on a patient's skin, they face a choice: monitor it for some time or remove it for biopsy. Similarly, when removing breast tumors, surgeons must send excised tissues... Read more
Copyright © 2000-2024 Globetech Media. All rights reserved.