Does ALS Stand for All is Lost Suddenly?
Amyotrophic lateral sclerosis, better known as ALS or Lou Gehrig’s disease, is a central nervous system disease where motor neurons are targeted. The motor neurons send signals to your muscles all over your body, even ones used to speak, swallow, and breathe. According to the Mayo Clinic website, ALS symptoms begin with muscle weakness in your hands, feet, and limbs, and continues to spread over time. As the disease progresses, the more vital processes such as breathing and speaking make living with the disease very difficult. Individuals that are diagnosed with ALS typically are told they have only a couple years left. However, this does not mean that it will always be the case. Genius Stephen Hawking has lived 50 years with ALS. So what causes this awful disease? What hope is there for those who are unfortunately diagnosed?
As of today, there is no certain answer as to what is the official cause of ALS. However, researchers have determined a few processes that are present in ALS patients. These processes are as follows:
Oxidative Stress and Mitochondrial Damage
Oxidative stress comes from a high amount of free radicals and not enough response to break down these free radicals. The body naturally has antioxidants and enzymes to regulate these free radicals, however, in ALS patients, the enzyme SOD1 typically used to relieve oxidative stress is mutated and cannot function properly. This oxidative stress causes the mitochondria to become damaged and RNA to be incorrectly spliced/metabolized. Below is an image of a motor neuron. The mitochondrion can be seen labeled toward the bottom (the little tan bean shaped organelles).
There are two RNA binding proteins called FUS and TDP43. Both of these proteins are supposed to be in the nucleus of a cell and interact with RNA to help in making more proteins properly. However, in ALS patients, FUS and TDP43 are removed from the nucleus and accumulate in the cytoplasm. Since they are no longer in their proper location, the proteins that they would have helped produce would no longer be made correctly, causing mayhem in the mitochondria. Since oxidative stress is highly localized in the mitochondria, the relocation of FUS and TDP43 can be linked to the cause of oxidative stress and mitochondrial damage.
Protein Folding and RNA Binding Proteins
FUS and TDP43 also have an effect on protein folding. There are certain chaperone proteins that allow other proteins to be imported into the mitochondria and allow the proteins to fold correctly. However, FUS and TDP43 can actually trap the necessary chaperones which does not allow the proteins to get where they need to be and are not folded correctly. If proteins are not folded correctly, they are unable to do their jobs and must be broken down by the cell. If there are too many misfolded proteins in the mitochondria, oxidative stress builds and the mitochondria is damaged, and RNA is not metabolized correctly.
As we can see, it seems that each of these causes discussed stems from and causes the others. Unfortunately because of this, no one knows where ALS truly originates, and it is almost impossible to know what exactly to target to treat this disease. One drug does exist that only extends life for 2-3 months, but this drug also costs $14,000.
It is never easy to hear a loved one has been diagnosed with an illness that has no known cause or cure. Coping can be difficult and your life is forever changed. I am confident, however, that our modern medicine and advancing research will, one day, find a way to treat or even cure this most unfortunate disease. For now, all we can do is hope. All is not lost suddenly.