#ScienceSaturday posts share exciting scientific developments and educational resources with the KAND community. Each week, Dr. Dominique Lessard and Dr. Dylan Verden of KIF1A.ORG summarize newly published KIF1A-related research and highlight progress in rare disease research and therapeutic development.

KIF1A Research

From the archives: Transport of a kinesin-cargo pair along microtubules into dendritic spines undergoing synaptic plasticity (2016)

Learning is a precious biological gift. Our nervous systems adapt to interpret and learn from their actions and the environment, a process called neuroplasticity. This adaptation occurs at synapses where one neuron’s axonal bouton (aka terminal) communicates to another neuron’s dendrite. Both axons and dendrites can grow or shrink in response to activity; these changes are tightly regulated so neurons can modify specific connections and promote learning. Neuroplasticity underlies learning new information and gaining muscle memory. This week’s #ScienceSaturday discusses how KIF1A plays a role in this process.

Synapse growth and remodeling (From Wikimedia Commons)

Researchers first imaged rat-derived neurons to show that KIF1A carries a cargo called syt-IV into dendrites. When a synapse is active, KIF1A enters the dendrite in events called “invasions”: microtubules form branches that enter individual dendrites, KIF1A carries syt-IV along those branches, and releases it to fuse with the plasma membrane. This orderly transport delivers syt-IV to specific locations in the dendrite. When KIF1A was knocked down, syt-IV floated into dendrites on its own in an unregulated manner, and sometimes fused before it was meant to. The presence of a slow mutant KIF1A kept syt-IV near the microtubule, so it couldn’t fuse to the plasma membrane at all. These transport disruptions caused the dendrites to form long thin processes instead of their normal button shape.

The authors concluded, “Although our understanding of synaptic plasticity has increased greatly over the years, it is still unknown how the strength of certain synapses is increased during plasticity, while other synapses are unaffected. Nevertheless, targeted trafficking of materials in and out of specific spines is a key component of synaptic plasticity.” Neuroplasticity is a lifelong process in our brain that allows us to learn from individual moments. One hope for therapeutics that restore healthy KIF1A function is that these adaptive mechanisms will function again.

Rare Roundup

FDA Releases Action Plan for Rare Neurodegenerative Diseases, Including ALS

The traditional structure of therapeutic research and development often leaves rare disease patients out of the picture. Addressing KAND and thousands of other rare diseases requires policy and regulatory changes that acknowledge our communities’ priorities and needs. The US Food and Drug Administration has released a new proposal to improve the infrastructure of developing therapeutics for rare neurodegenerative disorders. The five-year plan is intended to foster public-private partnerships, fund disease-specific treatment strategies and promote patient access to new treatments. KIF1A.ORG looks forward to continuing and deepening our engagement with the FDA to ensure the KAND community benefits from the new initiatives launched through this action plan.

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