Experimental and Atomistic Computational Studies of Mechano-Chemical Transport Processes Involved in Neurodegenerative Diseases

Abstract

One of the most studied neurodegenerative diseases is Alzheimer’s disease (AD), which consists of axonal degeneration caused by no correctly reaching of neurotransmitters to the synapse. This deficiency is because binding of kinesin heads onto microtubules (MTs) is hindered by the attachment of tau proteins on MTs near (or between) binding sites. Thus, early detection of changes in the kinesin-MT interaction can be used to predict the presence of an incipient stage of AD. To predict changes in mechano-chemical behavior, a computational model for the kinesin-MT system was constructed. In this paper, molecular dynamics simulations and experiments were performed to identify the micro-mechanical properties of the components of the model, e.g., the behavior of the MT region plus the neck linker structure under fluctuating forces and characteristics of kinesin transport on MT for a healthy MT.