Pathway in neurons may contribute to neurodegenerative disease

Source: Xinhua| 2017-10-05 06:43:26|Editor: Song Lifang
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CHICAGO, Oct. 4 (Xinhua) -- Researchers at the University of Michigan (UM) found that an injury pathway in the neurons of fruit flies may cause the loss of synapses in diseases such as Alzheimer's and ALS.

The pathway, called DLK, recently caught researchers' attention as a candidate drug target as it contributes to the deterioration of damaged neurons. And researchers further find that inhibiting DLK may help neurons to maintain working synapses.

The pathway studied in fruit flies is similar to the pathway in the neurons of mammals and humans. UM researchers have found a new relationship between the injury pathway and a protein in neurons called kinesin or Unc-104.

UM researchers found that the injury pathway is triggered and synapses become defective when Unc-104 is damaged or mutated, and turning off the neuronal injury pathway can restore the function of these mutant synapses.

To study the role of the kinesin and the injury pathway in the malfunction of synapses, the researchers used a confocal microscope and electrophysiology to measure how well the synapses were firing, and found that when the injury pathway is shut down, the function of that synapse was restored.

"That was really striking," said Catherine Collins, UM associate professor of molecular, cellular and developmental biology. "It told us that the axon injury pathway was causing these major problems in synapses."

The researchers found that the pathway becomes activated when the Unc-104 kinesin is impaired, and that once activated, the pathway shuts down the formation of many of the synaptic proteins which are normally transported in axons.

"We can actually see how impairment of kinesin is affecting things in cell bodies, synapses and neurons," Collins said. "When we turned down the injury pathway in the kinesin mutants, we could see a huge mass of synaptic proteins accumulating in the cell body. That led us to the idea that the injury pathway turns down the levels of many synaptic proteins, leading to synapse malfunction."

The findings imply that activation of the injury pathway has negative consequences for synapses, which are in line with recent findings published in Science Translational Medicine saying that the injury pathway may be activated in patients with neurodegenerative diseases ALS and Alzheimer's disease.

As restricting the pathway can delay symptoms of these diseases in mouse models, researchers have turned their attention to the pathway as a potential therapeutic target.

The study has been published in the journal eLife.