Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


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

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:

More articles from Studies and Analyses:

nachricht Diagnoses: When Are Several Opinions Better Than One?
19.07.2016 | Max-Planck-Institut für Bildungsforschung

nachricht High in calories and low in nutrients when adolescents share pictures of food online
07.04.2016 | University of Gothenburg

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: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>