NERVE CELLS: DEATH AND REGENERATIONPresentation Transcript
What causes Brain Cell Death in Parkinson’s patients? & Key Protein Discovered That Allows Nerve Cells to Repair Themselves CATALINA BAENA GÓMEZ JANUARY 2011
INTRODUCTION The regeneration of nerve cells after brain injury and the explanation for the death of brain cells in Parkinson’s patients (not related to gene mutations) are two of the current foci of research in the field of neuroscience. Developing drugs that activate the regeneration of damaged nerve cells is what currently attracts the interest of scientists in molecular studies that will clarify the transformations in the nerve cells in various neurological diseases. Today we know that since neurons have to last a lifetime, their key infrastructure, microtubules, must be extremely well organized and also be flexible, so it can be rebuilt after an injury. As for Parkinson's disease, which affects half a million people in United States, there is urgent need to find the exact cause by which brain cells die, in order to find effective treatments.
Activation of this protein led to changes in another protein called parkin, which is known to be mutated in hereditary Parkinson's. The altered parkin lacked the capacity to break down other proteins, leading to harmful clumps of unprocessed protein in the neuron. The scientists believe this accumulation leads to progressive neuron death, resulting in Parkinson's symptoms that worsen over time.
When the researchers blocked tyrosine kinase c-Abl activation, parkin function was preserved and neurons were spared, for that reason, they believe these studies provide sound rationale for moving forward with a preclinical trial of tyrosine kinase c-Abl inhibitors, with the goal of developing a potent therapeutic drug for slowing the progression of Parkinson's.
The discovery of a specific signaling mechanism that is only turned on by oxidative stress and is selective only to Parkinson's-affected neurons of the nigra-striatum area is a building block in the process of understanding the mechanism of the 95 percent of Parkinson's cases with no known cause .
OBSERVATION! Molecular mechanisms used to inhibit the action of harmful proteins may serve as a foundation for the creation of drugs that attack diseases.
A team of scientist from Penn State University looked inside dendrites in vivo by using a simple model organism, the fruit fly, whose nerve cells are similar to human nerve cells. They observed microtubules, key infrastructure of the cell, that is constantly growing, so that it can be rebuilt in response to injury. The team realized that there must be a set of proteins controlling just how the highways are laid down at key to keep all the microtubules pointing the same way.
They identified the proteins, which include the motor protein kinesin-2, and found that when these proteins were missing the microtubules no longer pointed the same way in dendrites; that is, their polarity became disorganized. The team tested whether these proteins play a role in the ability of neurons to respond to injury.
Most neurons are irreplaceable, and yet they have an incredible ability to regenerate their missing parts. So Apparently, kinesin-2 is a crucial protein for polarity maintenance and for the ability to set up a new highway system when neurons need to regenerate.
The scientists concluded that If the proteins that control the layout of microtubules, or carry cargo along them, do not function properly, they can become culprits in neurodegenerative diseases such as hereditary spastic paraplegia .
OBSERVATION! Understanding in detail the internal dynamics of nerve cells opens new doors to the possibility of designing therapies for cell regeneration in patients with neuronal damage and intensify the action of proteins that coordinate the distribution of microtubules in the cell.
Many neurodegenerative diseases are increasing every year, focusing the attention of scientists in therapeutic mechanisms that can counteract these diseases. For this reason both news mean important advances that bring the world one step closer to finding the ability to regenerate nerve cells in various neurodegenerative syndromes.
In the first news, the scientists found that blocking the activation of the tyrosine kinase c-abl, which in Alzheimer's patients is activated after oxidative stress in the striatum area of the brain, stops the alteration of the Parkin protein, which in its altered state in sick patients, generates the accumulation of harmful substances in the neuron that lead to its death. This means that if the scientist can develop drugs based on inhibitors of tyrosine kinase c-abl could be stopped the progression of Parkinson´s.
In the case of the second news, discover the relationship of kinesin-2 to the maintenance of polarity necessary for cell regeneration, and show how microtubules are rebuilt in healthy neurons in response to damage, are significant advances that could lead to developing synthesis mechanisms of kinesin-2 (probably lost in patients with degenerative damage) . This would not only stop the symptoms of degeneration in patients, but would also stop the disease at an early stage in which even they do not show serious damage in the nervous system.
The greatest importance of both news, for the medicine and for medicine students, is that both of them lead to the conclusion that only thoroughly understanding the internal behavior of cells and considering all possible variations of pathological process, will be possible to develop an accurate perspective of diseases and how they could heal.
Alzheimer’s Disease International. World Alzheimer Report 2010. On line: http://www.alz.co.uk/research/files/WorldAlzheimerReport2010ExecutiveSummary.pdf
Key Protein Discovered That Allows Nerve Cells to Repair Themselves ScienceDaily (Jan. 1, 2011)
What Causes Brain Cell Death in Parkinson's Patients?
ScienceDaily (Jan. 7, 2011 )
¨There are billions of neurons in our brains, but what are neurons? Just cells. The brain has no knowledge until connections are made between neurons. All that we know, all that we are, comes from the way our neurons are connected¨ . Tim Berners-Lee