Ancient Worm Reveals Way to Destroy Toxic Cells in Huntington's Disease
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Ancient worm reveals way to destroy toxic cells in Huntington's disease
Associate Professor Roger Pocock, from the Monash Biomedicine Discovery Institute (BDI), and colleagues from the University of Cambridge led by Professor David Rubinsztein, found that microRNAs are important in controlling protein aggregates, proteins that have amassed due to a malfunction in the process of 'folding' that determines their shape.
[...] MicroRNAs, short strands of genetic material, are tiny but powerful molecules that regulate many different genes simultaneously. The scientists sought to identify particular microRNAs that are important for regulating protein aggregates and homed in on miR-1, which is found in low levels in patients with neurodegenerative diseases such as Parkinson's disease.
"The sequence of miR-1 is 100 per cent conserved; it's the same sequence in the Caenorhabditis elegans worm as in humans even though they are separated by 600 million years of evolution," Associate Professor Pocock said.
"We deleted miR-1 in the worm and looked at the effect in a preclinical model of Huntington's and found that when you don't have this microRNA there's more aggregation," he said. "This suggested miR-1 was important to remove Huntington's aggregates."
[...] "When you don't have miR-1, autophagy doesn't work correctly and you have aggregation of these Huntington's proteins in worms," Associate Professor Pocock said.
Professor Rubinsztein then conducted research which showed that the same microRNA regulates a related pathway to control autophagy in human cells.
"Expressing more miR-1 removes Huntington's aggregates in human cells," Associate Professor Pocock said.
Explore further
Interferon-I^2-induced miR-1 alleviates toxic protein accumulation by controlling autophagy, eLife (DOI: 10.7554/eLife.49930)
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