Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mutation in brain cells of descendants of Abraham Lincoln suggest he suffered from movement disorder

03.02.2006


Researchers at Johns Hopkins and the University of Minnesota have discovered a gene mutation in the descendants of Abraham Lincoln’s grandparents that suggests the Civil War president himself might have also suffered from a disease that destroys nerve cells in the cerebellum-- the part of the brain that controls movement. A report on this discovery will appear in the February print issue of Nature Genetics.



The joint finding of the SCA5 mutation comes over a decade after initial speculation that Lincoln might have suffered from Marfan disease. People with this inherited disorder are often tall and thin and can commonly have slender, tapering fingers. The identification of the Marfan gene at Hopkins (Nature 352, 279-81 [1991]) sparked debate concerning testing of President Lincoln’s DNA to determine whether his tall stature could have been caused by that disease.

The present discovery in Lincoln’s descendants of the gene that causes a movement disorder called spinocerebellar ataxia type 5 (SCA5), however, appears to offer much stronger evidence that the past president himself might have had SCA5, according to Jeffrey D. Rothstein, M.D., Ph.D., a professor of neurology and neuroscience and vice chairman for research in the Department of Neurology at The Johns Hopkins University School of Medicine. SCAs are neurodegenerative disorders that cause loss of coordination of limbs and eye movements, slurred speech and swallowing difficulties.


"Determining President Lincoln’s status relative to SCA5 would be of historical interest and would increase public awareness of ataxia and neurodegenerative disease," Rothstein said. The finding also has wider implications because similar mutations might also be associated with other neurodegenerative diseases, the Hopkins researcher said.

The researchers discovered that SCA5 is caused by a mutation of the ¥â-III spectrin gene SPTBN2, which disrupts the ability of certain nerves in the cerebellum to respond normally to incoming chemical signals. Eventually, these nerves -- called Purkinje cells -- degenerate, and the person loses fine control of the leg and arm muscles. This would explain historical descriptions of Lincoln’s uneven gait -- an early sign of ataxia -- according to the researchers. Ataxia is an inability to coordinate muscle activity in the arms and legs.

"The discovery by the team of the SCA5 mutations in 90 of 299 descendants of Lincoln could enable us to prove whether Lincoln himself carried the mutation by studying genetic material obtained from artifacts containing his DNA," said Rothstein, a co-author of the Nature Genetics paper.

The researchers found the mutation in all 90 affected individuals (ages 7 to 80 at time of exam) and in 35 descendants of Lincoln who had not yet started to show symptoms of SCA5 (ages 13 to 67 at time of exam), he said. The team also found two other types of mutations in ¥â-III spectrin 2 in a French and German family, respectively. The mutations found in the American, French and German families each affected a different part of the SPTBN2 gene, and thus knocked out a different part of the ¥â-III spectrin protein.

The mutation of the SPTBN2 gene disrupts the normal shape of ¥â-III spectrin, a protein that is key to the proper functioning of Purkinje cells, according to Rothstein, who cloned the protein in 2001 and first described its role in the brain. Specifically, ¥â-III spectrin helps to anchor another protein, called "glutamate transporter EAAT4," into the membrane of the Purkinje cell.

In the current study, the investigators showed in isolated cells that EAAT4 tends to migrate rapidly through the membrane of Purkinje cells. This movement disrupts the ability of the nerve-signaling chemical glutamate to bind with EAAT4, Rothstein said. "The loss of the ability of ¥â-III spectrin to anchor EAAT4 in place so it can respond to glutamate could lead to signaling abnormalities over time," said Rothstein. "And over time, that could cause Purkinje cell death and lead to the symptoms of SCA5."

A further implication of these findings is that SCA5 mutations could affect the complex movement of proteins in other nerve cells, the researchers said. Specifically, the spectrin’s interaction with a molecular "motor" that shuttles proteins through the cell suggests that mutated forms of this protein would disrupt this critical function.

The motor, which transfers proteins along cellular highways called microtubules, as well as glutamate transporters are implicated in a wide range of processes that are key to proper functioning of nerves, Rothstein noted. Disruption of the motor appears to occur in several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), he added. ALS is a fatal disease involving the cells in the brain and spinal cord that control muscles. Motor disruption also occurs in Huntington’s disease (HD), a genetic disorder that causes degeneration of brain cells in certain areas of the brain, resulting in uncontrolled movements, loss of intellectual abilities and emotional disturbance. In addition, disruption of protein transport through the long arms of nerves called axons occurs in Alzheimer’s disease, he added.

"The results of our work and that of other researchers suggest that even though different ¥â-III spectrin mutations disrupt different cellular processes, all of these different disruptions eventually cause the death of a particular brain cell," he said. "So further studies of SCA5 will likely provide insight into molecular mechanisms common to SCA5 and other neurodegenerative diseases. In recent years we have discovered drugs that can modulate the glutamate transporter and its gene, and that research could someday be useful for treating patients with spinocerebellar ataxia."

Eric Vohr | EurekAlert!
Further information:
http://www.jhmi.edu

More articles from Life Sciences:

nachricht Scientists unlock ability to generate new sensory hair cells
22.02.2017 | Brigham and Women's Hospital

nachricht New insights into the information processing of motor neurons
22.02.2017 | Max Planck Florida Institute for Neuroscience

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Microhotplates for a smart gas sensor

22.02.2017 | Power and Electrical Engineering

Scientists unlock ability to generate new sensory hair cells

22.02.2017 | Life Sciences

Prediction: More gas-giants will be found orbiting Sun-like stars

22.02.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>