Features Partner Sites Information LinkXpress
Sign In
Advertise with Us


12 Nov 2016 - 16 Nov 2016
16 Nov 2016 - 19 Nov 2016

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

By BiotechDaily 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 

Print article


Drug Discovery

view channel
Image: Positive alpha-synuclein staining of a Lewy body from a patient with Parkinson\'s disease (Photo courtesy of Wikimedia Commons).

Bifunctional Dimer Drugs Prove Effective in Parkinson's Disease Yeast Model

A team of Canadian neurodegenerative disease researchers used a yeast model system to identify novel drug compounds that were able to block the misfolding of alpha- synuclein (AS) protein, which characterizes... Read more


view channel
Image: A space-filling model of the anticonvulsant drug carbamazepine (Photo courtesy of Wikimedia Commons).

Wastewater May Contaminate Crops with Potentially Dangerous Pharmaceuticals

Reclaimed wastewater used to irrigate crops is contaminated with pharmaceutical residues that can be detected in the urine of those who consumed such produce. Investigators at the Hebrew University... Read more


view channel

Collaborative Agreement to Aid in Setting Guidelines for Evaluating Potential Ebola Therapy

Cooperation between an Israeli biopharmaceutical company and medical branches of the US government is designed to set ground rules for continued evaluation of an experimental therapy for Ebola virus disease. RedHill Biopharma Ltd. (Tel Aviv, Israel), a biopharmaceutical company primarily focused on development and c... Read more
Copyright © 2000-2016 Globetech Media. All rights reserved.