Huntington Disease Clue Discovered

Researchers have demonstrated that mutated huntingtin protein, but not normal huntingtin, activates a neuron-specific protein (JNK3) which inhibits fast axonal transport, a system used to shuttle proteins from the nerve cell body, where they are made, to the synaptic terminals, where they are needed. This discovery might help explain the curious nervous system specificity of Huntington disease, even though the huntingtin protein is expressed in other parts of the body. "Inhibition of neuronal transport is enough to explain what is happening in Huntington's," asserted Dr. Scott Brady, senior author of the report. Loss of delivery of materials to the synaptic terminals results in loss of transmission of signals from the neuron. Loss of signal transmission causes the neurons to begin to die back, leading to reduced transmissions, more dying back, and eventual neuronal cell death. This mechanism might also explain the late onset of the disease, Dr. Brady said. Activation of JNK3 reduces transport, but does not eliminate it. Young neurons have a robust transport system, but transport gradually declines with age. "If you take a hit when you're very young, you still are making more and transporting more proteins in each neuron than you need," Dr. Brady said. "But as you get older and older, the neuron produces and transports less. Each hit diminishes the system further. Eventually, the neuron falls below the threshold needed to maintain cell health." This work was reported online on June 14 in Nature Neuroscience. [Press release] [Nature Neuroscience article]
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