Genetic Basis of Neurodegeneration in Huntington’s Disease Identified

A genetic mechanism has been identified which causes an abnormal protein to result in neurodegeneration in Huntington’s disease.

A genetic mechanism has been identified which causes an abnormal protein to result in neurodegeneration in Huntington’s disease. This has been identified by researchers who are conducting experiments on fruit flies and believe that the finding will open the door for new treatment methods that would slow the progression of the disease.

Huntington’s disease is a rare inherited neurological disorder caused by a mutation in the gene for the huntingtin protein (htt) that causes a genetic “stutter”—an abnormally long number of repeats of the amino acid glutamine at one end of the protein.

The study led by Juan Botas conducted their experiments on a fruit fly called Drosophila where the researchers introduced the gene for full-length abnormal human htt and later examined its early effects on neural function in the flies.

The findings revealed that before the abnormal protein produced any toxic effects in the nuclei of neurons, it caused abnormally high transmission of chemical signals, called neurotransmitters, among neurons.

Such neurotransmitters were activated by a neuron across connections, called synapses, to its neighbour, thereby prompting a nerve impulse in the receiving neuron.

The study also found that the mutant htt caused neurodegeneration and degeneration in the flies’ motor ability.

However, the researchers were able to successfully suppress these abnormalities by introducing other mutations into the fly genome that either reduced neurotransmission or reduced the activity of pores called calcium channels in the membranes of neurons.

These channels could trigger neurotransmission by controlling the influx of calcium into neurons.

“The findings described in this report unveil a mechanism of pathogenesis for expanded htt that does not require its nuclear accumulation in detectable amounts,” wrote the researchers.

They also said that increased neurotransmission “likely represents a mechanism of pathogenesis taking place at early stages of disease progression.

Researchers believe that these findings can harbour potential therapies for delaying the onset and progression of the disease.

“These findings point to increased synaptic transmission as a therapeutic target with the potential of delaying [Huntington’s disease] onset and thus likely impacting disease progression,” they wrote.The study has been published in January 10 issue of the journal Neuron.

Source-ANI
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