King's College London, Institute of Psychiatry
Phosphorylation of kinesin light chain and calsyntenin-1/alcadein mediated axonal transport and processing of APP in Alzheimers disease
Alzheimer's Research UK
Neurons comprise cell bodies and wire-like processes called axons and dendrites that connect to each other at structures called synapses. There are up to 100 billion neurons and 100 trillion synapses in the human brain and this network enables the computing of information. Most neuronal proteins are made in the cell body and since axons and dendrites require proteins to function, they have to be transported from the cell body into and through the axons and dendrites to the synapse. This transport of protein cargoes involves molecular motors that run on rails and utilize a fuel called ATP. One key axonal motor is kinesin which moves along microtubule rails. As such, axonal transport is like a train journey with an engine (kinesin) using fuel to move cargoes along rails. We now know that axonal transport goes wrong in Alzheimers disease but it is not clear which aspect is defective. Like a train journey, there could be a problem with the engine, fuel supply, rails, signaling or even the cargoes themselves. We have discovered a new signaling pathway that has major implications for defective axonal transport in Alzheimers disease. This project is to study further, its role in Alzheimers disease.