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: Star-like glial cells in red surround alpha-beta plaques in the cortex of a mouse with a model of Alzheimer\'s disease (Photo courtesy of Strittmatter laboratory/Yale University).

Experimental Cancer Drug Reverses Symptoms in Mouse Model of Alzheimer's Disease

An experimental, but clinically disappointing drug for treatment of cancer has been found to be extremely effective in reversing the symptoms of Alzheimer's disease (AD) in a mouse model.... Read more

Biochemistry

view channel
Image:  Model depiction of a novel cellular mechanism by which regulation of cryptochromes Cry1 and Cry2 enables coordination of a protective transcriptional response to DNA damage caused by genotoxic stress (Photo courtesy of the journal eLife, March 2015, Papp SJ, Huber AL, et al.).

Two Proteins Critical for Circadian Cycles Protect Cells from Mutations

Scientists have discovered that two proteins critical for maintaining healthy day-night cycles also have an unexpected role in DNA repair and protecting cells against genetic mutations that could lead... Read more

Business

view channel

NanoString and MD Anderson Collaborate on Development of Novel Multi-Omic Expression Profiling Assays for Cancer

The University of Texas MD Anderson Cancer Center (Houston, TX, USA) and NanoString Technologies, Inc. (Seattle, WA, USA) will partner on development of a revolutionary new type of assay—simultaneously profiling gene and protein expression, initially aiming to discover and validate biomarker signatures for immuno-oncology... Read more
 

Events

21 Apr 2015 - 23 Apr 2015
21 Apr 2015 - 23 Apr 2015
Copyright © 2000-2015 Globetech Media. All rights reserved.