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




Molecular Interactions Identified That Block Protein Transfer into Mitochondria of Huntington's Disease Neurons

By LabMedica International staff writers
Posted on 08 Jul 2014
Print article
Image: A microscope image of a neuron with inclusion (stained orange) caused by Huntington\'s disease (Photo courtesy of Wikimedia Commons).
Image: A microscope image of a neuron with inclusion (stained orange) caused by Huntington\'s disease (Photo courtesy of Wikimedia Commons).
Researchers have identified a protein complex that interacts with the mutated form of huntingtin protein to impair transport of proteins into the mitochondria of brain cells, which leads to their malfunction and the loss of neurons that characterizes Huntington's disease.

Huntington’s disease is caused by a dominant gene that encodes a protein known as huntingtin (Htt). The 5' end of the Huntington's disease gene has a sequence of three DNA bases, cytosine-adenine-guanine (CAG), coding for the amino acid glutamine, that is repeated multiple times. Normal persons have a CAG repeat count of between 7 and 35 repeats, while the mutated form of the gene has anywhere from 36 to 180 repeats. The mutant form of Htt is broken down into toxic peptides, which contribute to the pathology of the syndrome.

Investigators at the Washington University School of Medicine (St. Louis, MO, USA) and their colleagues at the University of Pittsburgh (PA, USA) worked with in vitro culture models and with a mouse model that mimicked the early stages of Huntington's disease.

They reported in the May 18, 2014, online edition of the journal Nature Neuroscience that recombinant mutant Htt directly inhibited mitochondrial protein import in their culture model. Furthermore, mitochondria from the brain synaptosomes of presymptomatic Huntington's disease model mice and from mutant Htt-expressing primary neurons exhibited a protein import defect, suggesting that deficient protein import was an early event in Huntington's disease.

At the molecular level, the investigators spotted interactions between mutant Htt and the TIM23 (translocase of inner mitochondrial membrane 23) mitochondrial protein import complex. Overexpression of TIM23 complex subunits attenuated the mutant Htt–induced mitochondrial import defect and subsequent neuronal death, which demonstrated that deficient mitochondrial protein import caused mutant Htt-induced neuronal death.

“We showed the problem could be fixed by making cells overproduce the proteins that make this transfer possible,” said first author Dr. Hiroko Yano, assistant professor of neurological surgery, neurology, and genetics at the Washington University School of Medicine. “We do not know if this will work in humans, but it is exciting to have a solid new lead on how this condition kills brain cells.”

Related Links:

Washington University School of Medicine
University of Pittsburgh 


Platinum Member
COVID-19 Rapid Test
OSOM COVID-19 Antigen Rapid Test
One Step HbA1c Measuring System
GREENCARE A1c
POCT Fluorescent Immunoassay Analyzer
FIA Go
New
Gold Member
Systemic Autoimmune Testing Assay
BioPlex 2200 ANA Screen with MDSS

Print article

Channels

Clinical Chemistry

view channel
Image: Reaching speeds up to 6,000 RPM, this centrifuge forms the basis for a new type of inexpensive, POC biomedical test (Photo courtesy of Duke University)

POC Biomedical Test Spins Water Droplet Using Sound Waves for Cancer Detection

Exosomes, tiny cellular bioparticles carrying a specific set of proteins, lipids, and genetic materials, play a crucial role in cell communication and hold promise for non-invasive diagnostics.... Read more

Molecular Diagnostics

view channel
Image: The study showed the blood-based cancer screening test detects 83% of people with colorectal cancer with specificity of 90% (Photo courtesy of Guardant Health)

Blood Test Shows 83% Accuracy for Detecting Colorectal Cancer

Colorectal cancer is the second biggest cause of cancer deaths among adults in the U.S., with forecasts suggesting 53,010 people might die from it in 2024. While fewer older adults are dying from this... Read more

Hematology

view channel
Image: The Gazelle Hb Variant Test (Photo courtesy of Hemex Health)

First Affordable and Rapid Test for Beta Thalassemia Demonstrates 99% Diagnostic Accuracy

Hemoglobin disorders rank as some of the most prevalent monogenic diseases globally. Among various hemoglobin disorders, beta thalassemia, a hereditary blood disorder, affects about 1.5% of the world's... Read more

Microbiology

view channel
Image: The new platform is designed to perform blood-based diagnoses of nontuberculosis mycobacteria (Photo courtesy of 123RF)

New Blood Test Cuts Diagnosis Time for Nontuberculous Mycobacteria Infections from Months to Hours

Breathing in nontuberculous mycobacteria (NTM) is a common experience for many people. These bacteria are present in water systems, soil, and dust all over the world and usually don't cause any problems.... Read more

Industry

view channel
Image: These new assays are being developed for use on the recently introduced DxI 9000 Immunoassay Analyzer (Photo courtesy of Beckman Coulter)

Beckman Coulter and Fujirebio Expand Partnership on Neurodegenerative Disease Diagnostics

Beckman Coulter Diagnostics (Brea, CA, USA) and Fujirebio Diagnostics (Tokyo, Japan) have expanded their partnership focused on the development, manufacturing and clinical adoption of neurodegenerative... Read more
Copyright © 2000-2024 Globetech Media. All rights reserved.