Amyotrophic lateral sclerosis (ALS), a disease made famous by Lou Gehrig, is the most common adult-onset motor neuron disease. Characterized by upper and lower neuron degeneration, ALS patients commonly present with spasticity and atrophy of the limbs since the neurons responsible for voluntary movement and muscle power are compromised.
The most common form of ALS is the sporadic form, making up 90 percent of patients, while the familial form only makes up 10 percent and is associated with several genes. The cause of ALS is still greatly undefined, but recent research has shown that calcium disturbances, endoplasmic reticulum stress, and mitochondrial stress may be implicated in the disease pathology.
Under normal conditions calcium levels are low inside our cells, and is stored in our endoplasmic reticulum (ER) and mitochondria. However, calcium is responsible for proper cell signaling, and signal transduction. Making it very important in nerve cells.
The ER is responsible for proper protein synthesis and folding. If proteins are misfolded they become dysfunctional and accumulate in the ER, causing ER stress. Protein synthesis starts at the ribosome; after the protein chain is put together by the ribosome it enters the lumen of the ER where proteins called chaperon proteins are able to guide the folding of the new protein. Chaperon proteins can also try and refold already misfolded proteins. Unfortunately, many chaperon proteins are negatively affected by calcium.
This is where researchers suggest ALS comes into the picture. Many wonder why only motor neurons are targeted in ALS, and this theory may answer the question. Motor neurons are more susceptible to calcium influx because they have more calcium permeable channels. Based on this new research the greater levels of calcium in these motor neurons negatively impact the proteins responsible for proper protein folding. Since proteins aren’t being folded properly, there is increased stress in the ER.
There are a number of proteins that are supposed to alleviate this stress, these proteins decrease regular protein synthesis and increase the level of proteins that can relieve this stress. But in ALS patients there is so much stress that extensive activation of this process eventually triggers apoptosis, or cell death.
So what can we actually do with this information?
This new research will serve as a way to develop pharmacological treatments. One way, suggested by the researchers, was to promote the proteins that are supposed to alleviate ER stress, but without inducing cell apoptosis. There are, however, many gaps in our knowledge about ALS and this mechanism, so even though we have potential, a lot has yet to be seen.
Unfortunatley, ALS is a fairly rapidly progressing disease, and the disease will typically take the patients life within 2 to 5 years after diagnosis. The fact that the disease only attacks motor neurons, not cognitive neurons like Alzheimer’s, makes the disease that much harder to watch.
We need to expand on this information about ALS, because at the moment, ALS seems to attack anyone, and we here time and time again that knowledge is power.
Knowledge is Power: power for muscles affected by ALS
