"KIF5A Gene Associated with the Development of ALS"

An international research team has identified a new gene, KIF5A, that they say is associated with the development of amyotrophic lateral sclerosis (ALS) which is also known as Lou Gehrig's Disease. ALS is a neuro-degenerative disease that over time, breaks down a person's ability to control or initiate muscle movement, in most cases leading to paralysis and death withing 2-5 years of diagnosis. It is caused by the breaking down of neurons in both the brain and spinal cord and about 10% of diagnosed patients are classified as "genetic" or "familial" in nature and caused by genetic defects while the other 90% are "sporadic" or without a direct family history.

According to the article this discovery will help advance the understanding of ALS and helps point a finger at the cytoskeleton as a focal point for potential new drug development. The cytoskeleton is the structure that makes up the axon which transfers electrical impulses and information through proteins. The cytoskeleton is where defects that are associated with or cause the effects of ALS can be found. KIF5A's job is to move signals up and down the cytoskelton within the axon, without KIF5A functioning properly, this important information is not able to be transferred. In addition to this KIF5A also plays an important role in mediating RNA transfer, and RNA processing also happens to be considered as a pathogenesis to ALS. This gene was discovered to be associated with ALS through 2 different, successful approaches which were financially supported by multiple organizations including the ALS Association.

Patients with this particular gene mutation are expect to live, on average, 10 years post diagnosis which is much longer than the average ALS patient. This information alone is huge for patients who wish to identify how much time they have. As someone who is dealing with my former coach/mentor/father figure's ALS diagnosis just over a year ago, and his subsequent physical struggles since, this is a small addition of hope that A) may lead to more useful research and information in the diagnosis and treatment of ALS and B) may allow him (if he chooses to) to be tested for this genetic defect to give some indication or forecast of how quickly this disease will affect him. One of the toughest parts of dealing with a loved one's ALS diagnosis is the uncertainty of how quickly the disease progresses. A guy that I went to grade school with passed away 4-5 years ago only 6 months after his diagnosis while in his early 20s, while we have seen in the case of Stephen Hawking, though rare, some people are able to survive a very long time with this disease. When you know your time left to see someone you care about is short, but you don't know how short, it can lead to tough decisions to be made for both the diagnosed and their loved ones. Having this first hand knowledge makes me think that this discovery is huge for ALS patients and their families and I am so hopeful for what may come next.



Link-
https://www.drugtargetreview.com/news/30715/kif5a-gene-als/

Additional link-
https://medicalxpress.com/news/2018-03-als-gene-common-role-cytoskeleton.html

Journal post of the study-
http://www.cell.com/neuron/fulltext/S0896-6273(18)30148-X

Worm Leads to Insight on Mystery About Neurons

     
     Scientist have discovered that the unc-16 gene of the roundworm Caenorhabditis elegans can restrict nerve fibers of the brain from clogging up.  The gene codes for a gatekeeper that restricts the flow of cellular organelles from the cell body to the axon, which is used for signaling.  The buildup of organelles at the axon can cause interference with neuron signaling and/or neuro degenerative disorders.  The study of the unc-16 gene brings to light that the breakdown of the gatekeeper may be the underlying cause of degenerative disorders.

     C.elegans is a small translucent roundworm that has only 300 neurons.  The use of the roundworm as a model organism in the study was beneficial because complex  genetic techniques and imaging methods are applicable due to its size and structure, unlike larger animals, where such techniques would be impossible.  Ken Miller’s laboratory team at the Oklahoma Medical Research Foundation tagged organelles with fluorescent proteins and then used time-lapse imaging to follow the movements of the organelles.   In normal axons, organelles exited the cell body and entered the initial part of the axon, but did not move further. In axons of the unc-16 mutants, the organelles rode on tiny motors that carried them deep into the axon, where they accumulated.

Research on simple organsims is important and even necessary. This is especially true in cases where we are unable to understand diseases and are unable to study them in larger, more complex organisms.  Studies and research with a simple model organism has led to greater insight on important degenerative disorders.  This research can ultimately lead to major discoveries for treatment and cures in the future.

http://www.newswise.com/articles/tiny-worm-sheds-light-on-giant-mystery-about-neuron

http://en.wikipedia.org/wiki/Axon

Nerve Regeneration

An article on Sci-news.com states that the gene required for nerve regeneration has been identified. Researchers at Penn State University, led by Professor Melissa Rolls, have found that axons regrow themselves when cut or damaged and that the process by which the axons repair themselves is completely shut down a certain mutation is present within the gene.

The team began by looking at microtubule-remodeling proteins. Microtubules are structural components of cells that allow basic building blocks to be transported. It has been previously suggested that these microtubules might need to be rebuilt in order to repair the axons, hence why the team began by investigating the role of those remodeling proteins in axon regrowth. From these proteins, the team focused on a cut that sever the microtubules into small pieces. From this set, they identified a protein called spastin.

The disease gene that makes the spastin protein is called SPG4. According to Professor Rolls, "When one copy of this gene is disrupted, affected individuals develop hereditary spastic paraplegia (HSP), which is characterized by progressive lower-limb weakness and spasticity as the long-motor axons in the spinal cord degenerate. Thus, identifying a new neuronal function for spastin may help us to understand this disease."

The gene used the fruit fly to study the spastin gene. The results showed that in the flies with one or two mutant copies of the gene (as opposed to having two normal copies) had no regrowth within cut axons. Not only this, but the team also discovered that the spastin gene has no role in the development of axons that were being assembled for the first time. Furthermore, they found that the dendrites were unaffected and continued to repair themselves even if the axon itself was not repaired. The researchers are continuing to do studies to see if other disease genes also play a role in nerve cell regeneration.

This discovery has opened up a huge amount of possibilities in humans. Since the experiment was performed on fruit flies, it is not known if this same thing happens in humans. However, I am sure that new studies will be performed to see if we can control the way axons are repaired. This is great news for anyone who has had nerve cell damage because we may be able to find a way to stimulate regrowth and help those who suffer.