Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Lou Gehrig's protein found throughout brain, suggesting effects beyond motor neurons

19.06.2008
Two years ago researchers at the University of Pennsylvania School of Medicine discovered that misfolded proteins called TDP-43 accumulated in the motor areas of the brains of patients with amyotropic lateral sclerosis (ALS), or Lou Gehrig's disease.

Now, the same group has shown that TDP-43 accumulates throughout the brain, suggesting ALS has broader neurological effects than previously appreciated and treatments need to take into account more than motor neuron areas. Their article appeared in last month's issue of the Archives of Neurology.

"The primary implication for ALS patients is that we have identified a molecular target for new therapies," says co-author John Q. Trojanowski, MD, PhD, Director of Penn's Institute on Aging. "The other implication is that new therapies for ALS now need to go beyond treating only motor neurons."

Traditionally, ALS has been diagnosed based on muscle weakness and neurodegeneration of the upper and lower motor neurons that extend from the motor cortex to the spinal cord and brainstem motor neurons, which directly innervate voluntary muscles. For example, if you want to wiggle your big toe, the signal travels from the motor neuron in the cortex at the top of your head to a synapse on the lower spinal cord motor neurons in the lower back, which, in turn transmit the "wiggle" command by sending a signal to the muscles that move your big toe. Patients with ALS cannot wiggle their big toe or complete other voluntary muscle movements, including those carried out by their other extremities and eventually, by the diaphragm that moves air in and of their lungs.

The study was conducted by examining post-mortem brain tissue of 31 ALS patients. The accumulation of TDP-43 was imaged by detecting TDP-43 with an antibody specific for this protein. TDP-43 pathology was observed not only in the areas of the brain and spinal cord that control voluntary movements, as expected, but also in regions of the brain that involve cognition, executive functioning, memory, and involuntary muscle control. TDP-43 pathology was not observed in any of the controls that did not have ALS.

The pathological TDP-43 observed in ALS brains is different in two ways from normal TDP-43 that is found in most cells. The ALS-associated TDP-43 includes fragments of normal TDP-43 as well as other abnormally modified forms of TDP-43, and it is located in the cytoplasm of neurons; whereas, normal TDP-43 is found almost exclusively in the cell nucleus. In ALS, the pathological TDP-43 accumulates in large "globs," mainly in cell bodies.

"Our observation of TDP-43 in the brains of ALS patients suggests that ALS and two other neurodegenerative diseases called ALS- PLUS [ALS with cognitive impairments] and FTLD [frontotemporal lobar disease] may all have the same underlying molecular pathology involving abnormal TDP-43," says Trojanowski. "This constitutes a paradigm shift in the way we think about these diseases."

Current research is focused on understanding the basic biology of TDP-43 in cell culture systems. The research team is now trying to find out whether pathological TDP-43 causes nerve cells to lose their normal function or if they take on a toxic function. "The over-riding goal that drives our work is helping ALS patients," says Trojanowski.

Felix Geser, of Penn, was lead author on this study. Linda Wong, Maria Martinez-Lage, Lauren Elman, Leo McCluskey, Sharon Xie, and Virginia Lee, all of Penn, and Nicholas Brandmeir, of Albany Medical College, Albany, NY were co-authors. This research was supported by grants from the National Institute on Aging.

PENN Medicine is a $3.5 billion enterprise dedicated to the related missions of medical education, biomedical research, and excellence in patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System.

Penn's School of Medicine is currently ranked #4 in the nation in U.S.News & World Report's survey of top research-oriented medical schools; and, according to most recent data from the National Institutes of Health, received over $379 million in NIH research funds in the 2006 fiscal year. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.

The University of Pennsylvania Health System includes three hospitals — its flagship hospital, the Hospital of the University of Pennsylvania, rated one of the nation's "Honor Roll" hospitals by U.S.News & World Report; Pennsylvania Hospital, the nation's first hospital; and Penn Presbyterian Medical Center — a faculty practice plan; a primary-care provider network; two multispecialty satellite facilities; and home care and hospice.

Karen Kreeger | EurekAlert!
Further information:
http://www.uphs.upenn.edu

More articles from Studies and Analyses:

nachricht Real-time feedback helps save energy and water
08.02.2017 | Otto-Friedrich-Universität Bamberg

nachricht The Great Unknown: Risk-Taking Behavior in Adolescents
19.01.2017 | Max-Planck-Institut für Bildungsforschung

All articles from Studies and Analyses >>>

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

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>