The finding concerns faults in a protein called FUS that plays an important role ferrying essential protein-building materials to cells in the brain and spinal cord.
The researchers behind the discovery, including members from the University of Toronto in Canada and the University of Cambridge in the UK, report their findings in the journal Neuron.
They suggest the study could be a major step forward in finding an effective treatment for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, a less common form of dementia that damages the frontal lobes of the brain.
Senior author and professor Peter St. George-Hyslop, a medical scientist, neurologist and molecular geneticist who leads research into neurodegenerative diseases at both universities, says:
"These are dreadful diseases - the more we know about how they work, the faster we'll find treatments or even a cure."
ALS - also known as Lou Gehrig's disease after the famous baseball player who succumbed to the disease - destroys motor neurons, the brain cells that control muscle movement.
People with ALS gradually get weaker and lose their ability to speak, swallow and breathe. Most only live for 2-5 years following diagnosis. The famous theoretical physicist Stephen Hawking - who has lived with ALS for over 50 years - is a rare exception.
In many cases, it appears that ALS is triggered by a build up of toxic proteins that kill neurons in the brain and spinal cord.
In recent years, researchers have also linked ALS to mutations in genes that code for RNA-binding proteins - molecules that attach to RNA (ribonucleic acid, which carries genetic information copied from DNA) to control many aspects of gene regulation: switching genes on and off, or increasing and decreasing their expression. RNA is also important for protein synthesis in cells.
'Irreversible fibrillar hydrogels throttles the nerve'
One RNA-binding protein affected by such mutations - called FUS - commonly builds up in the brain and spinal cord of ALS patients, but it was not thought to be a cause of the disease because it looks different from the clearly toxic clumps of tau, amyloid and alpha synuclein proteins that always form in diseases like Alzheimer's, Parkinson's and some forms of dementia.
In healthy individuals, FUS normally plays an important role transporting essential chemicals and signals in the brain and spinal cord. It shares a unique feature with some other RNA-binding proteins that sets them apart from the average.
The distinguishing feature is the ability to change from a liquid to a gel and back to a liquid. It seems that this property helps FUS amass materials that nerve cells require to make new proteins and deposit them in neat packages at the perimeter of the cells.
When in transit, FUS takes the form of a gel, and when it is shedding its cargo, it transforms into a liquid.
This unique feature appears to be important for specific parts of cells to obtain the precise materials they need speedily and efficiently - especially very big cells, such as those in the spinal cord, which can be more than a meter long.
The team found that a mutation in the gene that codes for FUS affects its ability to transform from a gel into a liquid. Mutated FUS forms very thick "irreversible fibrillar hydrogels" that do not morph back into liquids. Prof. St. George-Hyslop explains the effect this has:
"This kills the nerve by throttling it and preventing it from making new protein in the parts of the cell that desperately need it. The mutations force the gelling process to go further than it should have gone."
The researchers believe a solution may be found in preventing over-thickening - or reversing solidification - of the gel. This could be a way forward for an effective treatment for ALS and frontotemporal dementia - both diseases where mutations in FUS lead to this effect.
The discovery may also provide a way forward for other types of ALS where other gel-forming RNA-binding proteins also solidify, they conclude.
The study follows an earlier discovery that Medical News Today reported in January 2015, where, in the journal Cerebral Cortex, researchers describe finding a cell mechanism that plays a key role in ALS.
That discovery concerns upper motor neurons, a small group of brain cells that is vital for initiating and modulating voluntary movement and is especially vulnerable to degeneration. The researchers found that increasing stress in the endoplasmic reticulum - a cell component that makes proteins and lipids - can lead to upper motor neuron death.