Washington: Scientists claim to have discovered the common cause of all forms of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease that paralyses its victims.
The underlying disease process of ALS has long eluded doctors and prevented development of effective therapies.
Now, a team at Northwestern University has for the first time discovered that the basis of the disorder is a broken down protein -- identified as ubiquilin2 -- recycling system in the neurons of the spinal cord and the brain.
Optimal functioning of the neurons relies on efficient recycling of the protein building blocks in the cells. In ALS, that recycling system is broken. The cell can`t repair or maintain itself and becomes severely damaged.
In fact, ubiquilin2`s critical job is to recycle damaged or misfolded proteins in motor and cortical neurons and shuttle them off to be reprocessed. In people with ALS, it isn`t doing its job, the scientists found.
As a result, the damaged proteins and ubiquilin2 loiter and accumulate in the motor neurons in the spinal cord and cortical and hippocampal neurons in the brain. The protein accumulations resemble twisted skeins of yarn and cause the degeneration of the neurons.
The discovery, published in the journal Nature, provides a common target for drug therapy and shows that all types of ALS are, indeed, tributaries, pouring into a common river of cellular incompetence.
"This opens up a whole new field for finding an effective treatment for ALS. We can now test for drugs that would regulate this protein pathway or optimise it, so it functions as it should in a normal state," team leader Teepu Siddique said.
The discovery of the breakdown in protein recycling may also have a wider role in other neurodegenerative diseases, specifically the dementias, say the scientists.
This breakdown occurs in all three forms of ALS: hereditary, which is called familial; ALS that is not hereditary, called sporadic; and ALS that targets the brain, dementia.