Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING LLC
GLOBETECH PUBLISHING LLC
GLOBETECH MEDIA

Liver X Receptor Identified as Therapeutic Target for Treatment of Parkinson's Disease

By BiotechDaily International staff writers
Posted on 06 Sep 2012
Neurologists seeking means to prevent or treat Parkinson's disease have found that a protein receptor expressed on the microglial cells that surround dopamine-producing neurons plays a critical role in preventing the development of the disease.

The receptor protein studied by investigators at the University of Houston (TX, USA) is liver X receptor beta (LXRbeta). The liver X receptors (nuclear receptor subfamily 1, group H, member 2), LXRalpha and LXRbeta, form a subfamily of the nuclear receptor superfamily and are key regulators of macrophage function, controlling transcriptional programs involved in lipid homeostasis and inflammation. The inducible LXRalpha is highly expressed in liver, adrenal gland, intestine, adipose tissue, macrophages, lung, and kidney, whereas LXRbeta is ubiquitously expressed.

To determine the function of LXRbeta in brain tissues the investigators genetically engineered a line of mice lacking the gene for synthesis of this receptor. These modified mice and a matching group of normal, wild type mice were then exposed to the drug 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which is a neurotoxin that damages the brain in ways that closely mimic Parkinson's disease.

Results published in the July 23, 2012, online edition of the journal Proceedings of the National Academy of Sciences of the USA (PNAS) revealed that the dopamine-producing neurons of the substantia nigra of the genetically engineered mice were much more severely affected by MPTP than were those of the wild type controls. In addition, the number of activated microglia and astrocytes was higher in the substantia nigra of the modified mice than in the controls. Administration of the LXR-activating drug GW3965 to MPTP-treated control mice protected against loss of dopamine-producing neurons and fibers projecting to the striatum, and resulted in fewer activated microglia and astroglia.

"LXRbeta performs an important function in the development of the central nervous system, and our work indicates that the presence of LXRbeta promotes the survival of dopaminergic neurons, which are the main source of dopamine in the central nervous system," said senior author Dr. Jan-Ake Gustafsson, professor of biosciences and nutrition at the University of Houston. "The receptor continues to show promise as a potential therapeutic target for this disease, as well as other neurological disorders."

"LXRbeta is not expressed in the dopamine-producing neurons, but instead in the microglia surrounding the neurons," said Dr. Gustafsson. "Microglia are the police of the brain, keeping things in order. In Parkinson's disease the microglia are overactive and begin to destroy the healthy neurons in the neighborhood of those neurons damaged by MPTP. LXRbeta calms down the microglia and prevents collateral damage. Thus, we have discovered a novel therapeutic target for treatment of Parkinson's disease."

Related Links:
University of Houston


Channels

Drug Discovery

view channel
Image: Molecular model of the protein Saposin C (Photo courtesy of Wikimedia Commons).

Nanovesicles Kill Human Lung Cancer Cells in Culture and in a Mouse Xenograft Model

Nanovesicles assembled from the protein Saposin C (SapC) and the phospholipid dioleoylphosphatidylserine (DOPS) were shown to be potent inhibitors of lung cancer cells in culture and in a mouse xenograft model.... Read more

Biochemistry

view channel

Possible New Target Found for Treating Brain Inflammation

Scientists have identified an enzyme that produces a class of inflammatory lipid molecules in the brain. Abnormally high levels of these molecules appear to cause a rare inherited eurodegenerative disorder, and that disorder now may be treatable if researchers can develop suitable drug candidates that suppress this enzyme.... Read more

Lab Technologies

view channel
Image: The FLUOVIEW FVMPE-RS Gantry microscope (Photo courtesy of Olympus).

New Multiphoton Laser Scanning Microscope Configurations Expand Research Potential

Two new configurations of a state-of-the-art multiphoton laser scanning microscope extend the usefulness of the instrument for examining rapidly occurring biological events and for obtaining images from... Read more

Business

view channel

Roche Acquires Signature Diagnostics to Advance Translational Research

Roche (Basel, Switzerland) will advance translational research for next generation sequencing (NGS) diagnostics by leveraging the unique expertise of Signature Diagnostics AG (Potsdam, Germany) in biobanks and development of novel NGS diagnostic assays. Signature Diagnostics is a privately held translational oncology... Read more
 
Copyright © 2000-2015 Globetech Media. All rights reserved.