NAT10 defence for genetic disease?
Monday April 30th, 2018
A potential target has been identified that could benefit sufferers of a rare genetic disease that causes premature ageing.
Researchers at the University of Cambridge, England, believe that chemical inhibition or genetic deregulation of the enzyme N-acetyltransferase 10 (NAT10) leads to significant health and lifespan gains in a mouse model of Hutchinson-Gilford Progeria Syndrome (HGPS).
The study authors describe how the disease arises from specific mutations in the gene for the protein Lamin A. It results in a shorter, dysfunctional protein that accumulates in cells, specifically in the membranes surrounding the nucleus. This causes disorganisation of chromatin, deregulated transcription, accumulation of DNA damage and defective cell proliferation.
The researchers previously identified remodelin as an effective ameliorative agent and went on to ascertain that it was the enzyme N-acetyltransferase 10 (NAT10) that was affected by it.
In this new study, which is published in Nature Communications, the scientists wanted to establish if inhibiting NAT10, either chemically by administration of remodelin or genetically by engineering reduced production of NAT10, could ameliorate the disease in a mouse model with the same genetic defect as HGPS patients.
They found that it significantly improved the health of the diseased mice, increased their lifespan, and reduced the effects of the HGPS mutation across a variety of measures in body tissues and at the cellular level.
Senior author Professor Steve Jackson said: "We're very excited by the possibility that drugs targeting NAT10 may, in future, be tested on people suffering from HGPS. I like to describe this approach as a 're-balancing towards the healthy state'.
"We first studied the cell biology to understand how the disease affects cells, and then used those findings to identify ways to re-balance the defect at the whole-organism level. Our findings in mice suggest a therapeutic approach to HGPS and other premature ageing diseases."
Targeting of NAT10 enhances healthspan in a mouse model of human accelerated aging syndrome Nature Communications 27 April 2018; doi:10.1038/s41467-018-03770-3
Tags: Elderly Health | Genetics | UK News
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