Corporate Banner
Satellite Banner
Stem Cells, Cellular Therapy & Biobanking
Scientific Community
Become a Member | Sign in
Home>News>This Article

Single Gene Mutation Linked to Neurological Disorders

Published: Wednesday, October 16, 2013
Last Updated: Wednesday, October 16, 2013
Bookmark and Share
Mutation could offer insights into Alzheimer’s, Parkinson’s and Huntigton’s Diseases.

A research team says a gene mutation that causes a rare but devastating neurological disorder known as Lesch-Nyhan syndrome appears to offer clues to the developmental and neuronal defects found in other, diverse neurological disorders like Alzheimer's, Parkinson's and Huntington's diseases.

The findings, published in the Oct.9 issue of the journal PLOS ONE, provide the first experimental picture of how gene expression errors impair the ability of stem cells to produce normal neurons, resulting instead in neurological disease. More broadly, they indicate that at least some distinctly different neurodevelopmental and neurodegenerative disorders share basic, causative defects.

The scientists say that understanding defects in Lesch-Nyhan could help identify errant processes in other, more common neurological disorders, perhaps pointing the way to new kinds of therapies.

Lesch-Nyhan syndrome is caused by defects in the HPRT1 gene (short for hypoxanthine guanine phosphoribosyltransferace, the enzyme it encodes), a gene that is well-known for its essential "housekeeping duties," among them helping generate purine nucleotides - the building blocks of DNA and RNA.

Mutations in the gene result in deficiencies in the HPRT enzyme, leading to defective expression of the neurotransmitter dopamine and subsequent abnormal neuron function. HPRT mutation is known to be the specific cause of Lesch-Nyhan, an inherited neurodevelopmental disorder characterized by uncontrollable repetitive body movements, cognitive defects and compulsive self-mutilating behaviors. The disorder was first described in 1964 by medical student Michael Lesch and his mentor, William Nyhan, MD, professor emeritus at UC San Diego School of Medicine.

Using mouse embryonic stem cells modified to be HPRT-deficient, Friedmann and colleagues discovered that the cells do not develop normally. Instead, they differentiate from full-fledged neurons into cells that resemble and partially function as neurons, but also perform functions more typical of glial cells, a kind of supporting cell in the central nervous system. In addition, they noted that HPRT deficiency causes abnormal regulation of many cellular functions controlling important operational and reproduction mechanisms, DNA replication and repair and many metabolic processes.

"We believe that the neural aberrations of HPRT deficiency are the consequence of these combined, multi-system metabolic errors," said Friedmann. "And since some of these aberrations are also found in other neurological disorders, we think they almost certainly play some role in causing the neurological abnormalities in diseases like Alzheimer's, Parkinson's, Huntington's and possibly others. That makes them potential therapeutic targets for conditions that currently have limited or no treatments, let alone cures."

The task now is to further parse and better understand the many pathways that cause abnormal brain and brain cell development, and how those pathways are also disturbed in other neurological disorders. Those defects will probably not affect HPRT directly, said Friedmann, but rather will correspond to some of the same metabolic and genetic errors that occur as a result of HPRT deficiency. Once those pathways are identified, they may become good targets for more effective forms of therapy.

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,800+ scientific posters on ePosters
  • More than 4,000+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Artificial Kidney Research Gets A Boost
Development of a surgically implantable, artificial kidney — a promising alternative to kidney transplantation or dialysis for people with end-stage kidney disease — has received a $6 million boost.
Monday, November 09, 2015
Scientists Create CRISPR/Cas9 Knock-In Mutations in Human T Cells
In a project spearheaded by investigators at UC San Francisco, scientists have devised a new strategy to precisely modify human T cells using the genome-editing system known as CRISPR/Cas9.
Tuesday, July 28, 2015
Growing Spinal Disc Tissue
Scientists develop new method for growing spinal disc tissue in the lab for combating chronic back pain.
Friday, July 03, 2015
Grant Supports Creation of Patient-Derived Stem Cell Lines
Researchers have received a two-year, $600,000 grant from the National Institute on Aging to develop and study patient-derived stem cell lines.
Thursday, December 12, 2013
Prostate Cancer Stem Cells are a Moving Target
Researchers have discovered how prostate cancer stem cells evolve as the disease progresses, a finding that could help point the way to more highly targeted therapies.
Friday, December 06, 2013
Researchers Change Cell Types by Flipping a Single Switch
New findings have identified a method for changing one cell type into another in a process called forced transdifferentiation.
Friday, December 06, 2013
Understanding a Protein’s Role in Familial Alzheimer’s
Researchers have used genetic engineering of human iPSC’s to specifically and precisely parse the roles of a key mutated protein in causing familial Alzheimer's disease (AD).
Monday, November 18, 2013
Researchers Un-Junking Junk DNA
A study shines a new light on molecular tools our cells use to govern regulated gene expression.
Wednesday, November 13, 2013
$100M gift launches Sanford Stem Cell Clinical Center
T. Denny Sanford has committed $100 million to the creation of the Sanford Stem Cell Clinical Center at the University of California, San Diego.
Wednesday, November 06, 2013
Grafted Limb Cells Acquire Molecular ‘Fingerprint’ of New Location
Findings further creation of regenerative therapies for humans.
Wednesday, October 30, 2013
From Mature Cells to Embryonic-Like Stem Cells
Bioengineers have shown that physical cues can replace certain chemicals when nudging mature cells back to a pluripotent stage.
Tuesday, October 22, 2013
Researchers Develop Stem Cell Therapies for Acute Lung Injury
An estimated 200,000 patients a year have acute respiratory failure in the U.S. and mortality is about 30 to 40 percent.
Monday, October 21, 2013
Gene Repair Technique Could Have Many Applications
Using human pluripotent stem cells and DNA-cutting protein from meningitis bacteria, researchers have created an efficient way to target and repair defective genes.
Tuesday, August 13, 2013
Therapy Could Treat Breast Cancer that's Spread to Brain
Researchers have successfully combined cellular therapy and gene therapy in a mouse-model system to develop a viable treatment strategy for breast cancer that has spread to a patient's brain.
Tuesday, August 06, 2013
Scientists Streamline Production of Stem Cells
Researchers report a simple, easily reproducible RNA-based method of generating human induced pluripotent stem cells (iPSCs).
Friday, August 02, 2013
Scientific News
How a Genetic Locus Protects Adult Blood-Forming Stem Cells
Mammalian imprinted Gtl2 protects adult hematopoietic stem cells by restricting metabolic activity in the cells' mitochondria.
Fat Cells Originating from Bone Marrow Found in Humans
Cells could contribute to diabetes, heart disease.
Ancient Viral Molecules Essential for Human Development
Genetic material from ancient viral infections is critical to human development, according to researchers at the Stanford University School of Medicine.
CRI Identifies Emergency Blood-formation Response
Researchers report that when tissue damage occurs, an emergency blood-formation system activates.
New Way to Force Stem Cells to Become Bone Cells
Potential therapies based on this discovery could help people heal bone injuries or set hardware, such as replacement knees and hips.
Dead Bacteria to Kill Colorectal Cancer
Scientists from Nanyang Technological University (NTU Singapore) have successfully used dead bacteria to kill colorectal cancer cells.
Promise of Newborn Stem Cells to Revolutionize Clinical Practice
In this article Shweta Sharma, PhD, discusses the potential of an Umbilical Cord Blood bank as an untapped source of samples for research and clinical trials.
The Life Story of Stem Cells
A model analyses the development of stem cell numbers in the human body.
Novel Stem Cell Line Avoids Risk of Introducing Transplanted Tumors
Progenitor cells might eventually be used to repair or rebuild damaged or destroyed organs.
Advancing Genome Editing of Blood Stem Cells
Genome editing techniques for blood stem cells just got better, thanks to a team of researchers at USC and Sangamo BioSciences.
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos