#ScienceSaturday posts share relevant and exciting scientific news with the KAND community. This project is a collaboration between KIF1A.ORG’s Research Engagement Team Leader Alejandro Doval, President Kathryn Atchley and Chief Science Officer Dr. Dominique Lessard. Send news suggestions to our team at impact@kif1a.org.
Recent KIF1A-Related Research
GSK3beta impairs KIF1A transport in a cellular model of Alzheimer’s disease but does not regulate motor motility at S402
This week we are featuring a hot off the press publication from one of our Research Network members, the Silverman Lab at Simon Fraser University! In this study, regulation of KIF1A movement is being explored at the cellular level, meaning the majority of the experiments conducted in this paper use cells isolated from different animals to answer scientific questions. One of the first observations in this paper involves soluble amyloid-β oligomers (AbOs), a toxic substance connected to the progression of Alzheimer’s disease. When AbOs were administered to cells, KIF1A cellular transport was significantly impaired. How could this be happening? It turns out that another player in this cellular cast of characters called GSK3β can mediate this process.
Diving in further, from this study we learn that GSK3β physically alters KIF1A proteins by adding post-translational modifications (PTMs). What is a PTM? First, a “modification” in this context involves a structural change to a protein. In the case of KIF1A, GSK3β is adding a component to the KIF1A structure. This addition occurs “post-translationally” or after a KIF1A protein has been created. To sum it up, in this context, a specific component is being added to an already existing KIF1A protein. You can think of it like adding accessories to KIF1A!
Lastly, the specific type of PTM being added to KIF1A by GSK3β is called phosphorylation, or the addition of a molecule called a phosphate group. Phosphorylation occurs in many different proteins in our cells and is an important way that protein function is regulated. Because of this, learning more about the phosphorylation state of KIF1A is an intriguing topic to us, especially when thinking about molecular targets for therapeutic development. To learn more about phosphorylation, check out the video below. Thank you to the Silverman Lab for your work!
Rare Disease News
Ionis’ third novel antisense medicine for ALS, its first designed to treat a broad ALS population, begins clinical trial
This week our friends at Ionis Pharmaceuticals Inc. announced the start of a clinical trial for a third ALS antisense oligonucleotide (ASO) therapy. What makes this ASO different than other candidates? Like KAND, ALS can be heterogeneous in presentation and causation making it difficult to create a treatment strategy that caters to all patients. Intriguingly, this specific ASO targets a much greater breadth of patients that may be eligible for this treatment. Seeing progress in broad forms of treatment in diseases similar to KAND is encouraging to us as we work towards having the same option in the future. Congratulations to Ionis and the ALS community!
“As our third medicine designed to treat different forms of ALS to enter clinical trials, ION541 represents yet another example of the power of Ionis’ antisense technology to potentially target root causes of devastating neurodegenerative diseases.”
Frank Bennett, Ph.D., Ionis’ chief scientific officer
What Lies Between Grey and White in the Brain
You may be aware that our brains can be subdivided into different regions or lobes, each with their respective functions. Another way we can characterize regions of the brain is white matter vs. grey matter. The difference between white and grey matter has to do with which part of the neuron we are observing in an image of the brain. Grey matter is made up of cell bodies (or somas)—in the context of KIF1A, this is the area of the cell where cellular cargo is created and packaged up for transport. White matter however is made up of axons—this is an area in our neurons where KIF1A can engage in long distance cargo trafficking. Researchers out of the Max Plank Institute have recently used a special type of MRI to increase our understanding of brain white matter. What did they find using this new MRI technique? The white matter of our brains contains a lot of iron! Not only does this finding present new ways to take images of our brains but it also can increase our understanding of neurodegenerative conditions that involve the white matter. To learn more about the difference between white and grey matter in our brains, check out the video below!
[…] Furthermore, the authors go on to describe how specific mutations of tubulin can impair microtubule/kinesin relationships. Related to KAND, we learn that a specific mutation (D417) of tubulin (type TUBB2A) creates an environment where KIF1A cannot bind to the microtubule to engage in cargo transport. This highlights how important the tightly-tuned relationship between KIF1A and the microtubule must be for optimal cargo transport and neuronal health. Lastly, this paper discusses common therapeutic interventions involving microtubules, most of which are centered around stabilizing the microtubule tracks or targeting post-translational modifications, like we talked about in last week’s Science Saturday. […]