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In addition, the paper lays out the implications of distortedmitochondrial function on neuron health. Mitochondrial malfunctionis a known factor in non-infectious neurodegenerative conditionssuch as Alzheimer's disease and Parkinson's disease , Kramer said, though the pathway to this disruption is notentirely known. "Our model raises some new and exciting possibilities for futureresearch on other important human viruses that can invade thenervous system and cause disease," Kramer said. "And the fact that alpha-herpes infection damages the same keycellular function as neurodegenerative disorders also is striking,"he said. "Understanding how viral infection damages neurons mightgive us insight into how diseases like Alzheimer's do the same. Theviruses we study hijack well-studied cellular pathways that mightmake an effective target for future therapeutic strategies." In a healthy neuron, mitochondria move throughout the cell'selongated, tree-like structure to provide energy for variousprocesses that occur throughout the cell. For the strenuous task oflong distance intercellular communication, mitochondria move alongthe axon and synapses, sites of cell-to-cell contact wheresignaling occurs. Calcium plays a key role in this cell communication, Kramerexplained. A neuron experiences a spike in calcium levels in theaxon and synapses when it receives a signal from another neuron.Though a natural rover, mitochondria contain a protein called Mirothat detects this rush of calcium and stops the organelles in thesynapse. The mitochondria then provide energy as the cell passes asignal along to the next neuron. Through live-cell imaging of neurons grown in the Enquist lab,Kramer and Enquist observed how this process becomes corrupted byHSV-1 and PRV - and how the viruses need the process to spread. The chaos begins when the virus ramps up the neuron's firing ofelectrical signals, as was first reported in a 2009 paper publishedin the journal PLoS Pathogens by Enquist; first author Kelly McCarthy, a past member ofEnquist's lab who received her doctoral degree from Princeton in2011; and David Tank, the Henry L. Hillman Professor of MolecularBiology and co-director of the Princeton Neuroscience Institute. In the latest research, Kramer and Enquist found that this spike inelectrical activity floods the axon and synapses with calcium. As aconsequence, the Miro proteins detect the increase in calcium andstop mitochondrial motion. The virus' control over the cellimmediately dropped off, however, when Kramer and Enquistinterfered with Miro's ability to respond to the uptick in calciumlevels. Though the viral infection was not completely disrupted, itcould not spread within or to other cells with the same efficiency. Based on these observations, Kramer and Enquist suggest thatviruses such as HSV-1 and PRV may bring mitochondria to astandstill in order to hijack their transportation. Mitochondriamove about the neuron on the backs of motor proteins dynein andkinesin-1. During viral infection, mitochondria shed these proteinsto stop moving when Miro detects an upsurge in cellular calcium. Previous research has shown that HSV-1 and PRV also use kinesin-1specifically for transport within an infected cell. Thus, Kramersaid, his and Enquist's work suggests that it is very likely thatthe viruses disrupt mitochondrial motility so that they can hitchthemselves to the now available kinesin-1 proteins and move throughthe nervous system more efficiently. James Alwine, a University of Pennsylvania professor of cancer biology, said that the Princeton research is a significantcontribution to a growing body of research that describes howviruses seize cellular motor proteins such as kinesin-1. While the findings have therapeutic potential - particularly inhelping show how balancing cellular calcium might subdue viralinfection - the demonstration that viruses can move through aninfected cell with the ease of something as essential asmitochondria is notable in itself, said Alwine, who is familiarwith the research but had no role in it. "Determining the specific mechanism by which Miro function isabrogated may provide additional therapeutic avenues, but this alsois marvelous basic research that does not have to be justified byits therapeutic potential," he said. "To disrupt the loading of mitochondria to motor proteins so thatvirions [complete virus particles] can load instead is a clever wayfor a virus to be transported and is a great new idea provoked bythis data," Alwine said. "While other neurotropic viruses wouldhave to be tested specifically, movement in nerve cells is requiredby all of them. Thus, this observation provides a starting placeand a model mechanism for research with those other pathogens." Additional References Citations. The e-commerce company in China offers quality products such as China Salon Hair Clips , Salon Trolley Cart, and more. For more , please visit Round Hair Brush today!
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