Navigation Links
Lou Gehrig's protein found throughout brain, suggesting effects beyond motor neurons
Date:6/16/2008

PHILADELPHIA - 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.


'/>"/>

Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert  

Related medicine news :

1. Draining away brains toxic protein to stop Alzheimers
2. Penn study finds pro-death proteins required to regulate healthy immune function
3. New prion protein discovered by Canadian scientists may offer insight into mad cow disease
4. Emory researchers identify signaling protein for multiple myeloma
5. Human C-reactive protein regulates myeloma tumor cell growth and survival
6. Lowering Blood Protein Wont Help Kidney Patients
7. Blood protein detects lung cancer, even at earliest stage
8. Natural Protein Could Help Spot, Treat Liver Cancer
9. Heat shock proteins are co-opted for cancer
10. How adhesive protein causes malaria
11. Loss of gene leads to protein splicing and buildup of toxic proteins in neurons
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Lou Gehrig's protein found throughout brain, suggesting effects beyond motor neurons
(Date:6/20/2017)... ... June 20, 2017 , ... ... that the introduction of school choice can promote economic development in economically distressed ... that has, according to the report, contributed to the economic development of the ...
(Date:6/20/2017)... ... June 20, 2017 , ... AMC Health , ... and success in the clinical trials market. Similar to its approach in demonstrating positive ... the clinical trials marketplace by proving the value of eVisits to support virtual studies. ...
(Date:6/20/2017)... Midlothian, VA (PRWEB) , ... June 20, 2017 , ... ... latest in three-dimensional imaging technology with the VATECH PaX-i and Anatomage systems. With advanced ... oral cavity so they can place dental implants precisely and restore oral health for ...
(Date:6/20/2017)... ... June 20, 2017 , ... As a leading dental practice, Wall Centre Dental ... gum disease. Those with bleeding gums in Vancouver, BC, may be developing gingivitis, the ... to heart disease, stroke and diabetes. Drs. Parviz Roshan, Siamak Tehrani and Milton Reskovich ...
(Date:6/20/2017)... ... June 20, 2017 , ... New, state-of-the-art magnetic resonance imaging ... physicians with advanced capabilities for diagnosing and treating disease. , Jefferson’s Siemens ... to get a more accurate look inside the patient’s body. The new scanner ...
Breaking Medicine News(10 mins):
(Date:6/7/2017)... DUBLIN , June 7, 2017 Endo ... on June 7, 2017, the Hon. Joseph R. ... District of West Virginia , entered ... Systems, Inc. Pelvic Repair System Products Liability Litigation (the ... filed MDL cases to provide expert disclosures on specific ...
(Date:6/5/2017)... 5, 2017 Kohll,s Pharmacy & Homecare is the first ... United States . The Raizer is a simple battery ... up to an almost-standing position within a few ... one assistant and does not require any extra effort ... a child can operate it, and lightweight and ...
(Date:5/30/2017)... May 30, 2017 DarioHealth Corp. (NASDAQ: DRIO), a leading ... today announced that it will be presenting at the 7th annual ... PT. Erez Raphael , CEO, of DarioHealth will be giving ... be held on June 6th & 7th, 2017 at the Luxe ... small / micro-cap space. About ...
Breaking Medicine Technology: