#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 Science Communication Director Dr. Dominique Lessard. Send news suggestions to our team at firstname.lastname@example.org.
Recent KIF1A-Related Research
Computational analysis of hereditary spastic paraplegia mutations in the kinesin motor domains of KIF1A and KIF5A
While certain pathogenic variants of KIF1A have historically been associated with hereditary spastic paraplegia (HSP), KIF1A is not the only kinesin motors with HSP-associated variants. Another motor with HSP-associated variants is KIF5A, a member of the kinesin-1 family. While KIF1A and KIF5A can perform different roles in the cell, have different behavioral characteristics, and can transport different cargo they do have one thing in common: parts of their molecular structure. This is the case for many in the kinesin superfamily of proteins, where we find a higher level of structural conservation between different KIFs and kinesin families. What does this mean? It means that, while performing different biological functions, there are a lot of structural aspects that are consistent, or conserved, between kinesins especially in the motor domain. This conservation is an important parameter that helps us understand two main concepts about kinesin structure: 1) why certain structures are important to kinesin function as a whole and 2) how differences between kinesin protein structure lead to different biological capabilities.
In this article, the authors take a computational approach to understand the structural impact of certain mutations in KIF1A or KIF5A. Specific to KIF1A, it was discovered that the E253K mutation decreases the protein stability of kinesin motor domains. Furthermore, K253N and R280C mutations of KIF5A can destabilize the motor’s interaction with the microtubule track. These findings support the idea that when considering the impact of pathogenic KIF1A variants, we can potentially learn a lot from other kinesin motors!
Rare Disease News
Newly discovered ‘support system’ for axons suggests a novel therapeutic target for neurodegenerative diseases
Healthy neurons are essential for physiological processes in our bodies and for our overall health. So what types of support do neurons receive to ensure that they are functioning properly and can respond appropriately to certain types of neuronal damage? One type of support comes in the form of Schwann cells, a cell type found in our peripheral nervous system (PNS; the nerves outside of our brain and spinal cord). Schwann cells are considered to be glial cells, a category of non-neuronal cell types in our nervous system that help support neuronal function. In our PNS, Schwann cells encapsulate and wrap around the axons of neurons creating a substance called myelin. By creating myelin, Schwann cells help insulate axons and increase the efficiency of electrical signaling between neurons. This article features recent work out of the University of Buffalo highlighting a different role for Schwann cells in our PNS by helping our neurons respond to stress. It turns out that when neurons are in a stressful state, they crave a specific molecule produced by Schwann cells: sugar! By providing sugar molecules, Schwann cells are able to energetically support neurons through stressful environments highlighting a way in which injured axons are able to be soothed and repaired by the surrounding cellular environment. Interested in learning more about Schwann cells and myelin? Check out the video below!
Using telehealth to revolutionize the speed of making rare disease diagnoses
We’ve shared quite a few articles highlighting the increased usage of telehealth since the beginning of the COVID-19 pandemic. While there are clear trade offs, this article makes a compelling case as to why telehealth can decrease the time lag in making a rare disease diagnosis. Specifically, the Children’s National Hospital in Washington D.C. has “been working with Microsoft to pioneer the use of telegenetic consultations for patients and, more specifically, for those who are searching for a diagnosis, potentially for a rare disease.” This program uses inventive tools to increase the visibility of patients to rare disease teams and connects patients to specialists more quickly. Click the button below to read more about the five things learned from this pilot program so far!
“When health care providers are able to see patients in their home environments, it opens the door for more personal and honest discussions around their day-to-day struggles. Providers are able to form better connections with families by observing them at home, noticing behaviors that may not occur in a clinical setting, and recommending changes that can lead to more positive health outcomes.”
Stakeholders call for regulatory clarity in rare disease research network
The U.S. Food and Drug Administration’s Rare Disease Cures Accelerator recently put out a call for input centered around how the FDA and other agencies can support a more efficient timeline for rare disease drug discovery. KIF1A.ORG was one of many patient-advocacy associations that responded to this call with our ideas, suggestions, and concerns. Common themes and immediate needs expressed by stakeholders include better foundational science, more clinical trial readiness, and the robust collection of high-quality data. We are thankful for the FDA RDCA for giving our organization an opportunity to voice our thoughts and help create meaningful solutions. Read the article to learn more about this call for input!