Marathon molecule could accelerate the race for new neurological treatments

Scientists at the University of Warwick have discovered a new process that sets the fastest molecular engine in its marathon races in our neurons.

The results, now published in Nature Communications, opens the way to new treatments for certain neurological disorders.

The research focuses on KIF1C: a tiny, protein-based molecular motor that travels along microscopic tubular tracks (called microtubules) into neurons. The motor converts chemical energy into mechanical energy used to transport various cargo along the microtubule tracks, which is necessary to maintain adequate neurological function.

Neurons are cells that form the basis of our nervous system and provide the vital function of signal transfer between the brain, spinal cord and the rest of the body. They consist of a soma, dendrites and an axon, a long projection of the cell that carries signals to other neurons.

Molecular engines must remain inactive and park until their cargo is loaded on them. Neurons are an unusually long type of nerve cell (up to 3 feet) and, because of this marathoner distance, these tiny molecular motors must continue until their cargo is delivered at the end.

Inadequate freight transport is a crucial cause of some debilitating neurological disorders. Defective KIF1C molecular motors are the cause of hereditary spastic paraplegia, which affects approximately 135,000 people worldwide. Other studies have also shown links between faulty molecular motors and neurological disorders such as Alzheimer's disease and dementia.

Research shows how, without loading, KIF1C prevents itself from attaching itself to the microtubule tracks by folding back on itself. Scientists have also identified two proteins: PTNPN21 and Hook3, which can bind to the molecular engine KIF1C. These proteins deploy KIF1C, activating it and allowing the engine to attach and run along the microtubule tracks, as if shooting with the starting gun for the marathon.

The newly identified activators of KIF1C could stimulate the transport of cargo in the defective nerve cells of patients with hereditary spastic paraplegia, a possibility currently being explored by the team.

Anne Straube, of Warwick Medical School, commented on the future impact of this research: "If we understand how to turn off and on the engines, we may be able to design cellular transport machines with modified properties. with defective cellular transport to compensate for defects.You can also use nanotechnology to build new materials by exploiting their ability to concentrate enzymes or chemical reagents.We also study the properties of motors with mutations of patients in order to understand their functioning less good.

"We still know very little about how the motors are regulated.There are 45 kinesins expressed in human cells, but we only have an idea of ​​how the motors are activated only for a handful of them, it's the most versatile: it can efficiently transport cargo in all the processes of a neuron, not just the axon. "