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.

Their findings were published in eLife on December 4, 2019.

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 Parkinsons disease.

The sequence of miR-1 is 100 percent conserved; its 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 Huntingtons and found that when you dont have this microRNA theres more aggregation, he said. This suggested miR-1 was important to remove Huntingtons aggregates.

The researchers then showed that miR-1 helped protect against toxic protein aggregates by controlling the expression of the TBC-7 protein in worms. This protein regulates the process of autophagy, the bodys way of removing and recycling damaged cells and is crucial for clearing toxic proteins from cells.

When you dont have miR-1, autophagy doesnt work correctly and you have aggregation of these Huntingtons 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 Huntingtons aggregates in human cells, Associate Professor Pocock said.

Its a novel pathway that can control these aggregation-prone proteins. As a potential means of alleviating neurodegenerative disease, its up there, he said.

Additional work by Associate Professor Pococks colleagues showed that when human cells are supplied with a molecule called interferon-b the miR-1 pathway is upregulated, revealing a way of manipulating it.

He said the studies demonstrated the fundamental importance of discovery research. We asked a fundamental biological question to dissect a molecular mechanism that now is shown to be really important for potential therapies.

The researchers have provisionally patented their findings and are in discussions with pharmaceutical companies about translating the research. They will further test it in preclinical models for Huntingtons and Parkinsons disease.

Reference: Interferon--induced miR-1 alleviates toxic protein accumulation by controlling autophagy by Camilla Nehammer, Patrick Ejlerskov, Sandeep Gopal, Ava Handley, Leelee Ng, Pedro Moreira, Huikyong Lee, Shohreh Issazadeh-Navikas, David C Rubinsztein and Roger Pocock, 4 Dcember 2019, eLife.DOI: 10.7554/eLife.49930

This research was supported by the Australian NHMRC.

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Ancient Worm Reveals Way to Destroy Toxic Cells Potential New Therapy for Huntingtons and Parkinsons - SciTechDaily