From Antitubulins to Trackins

Abstract

Microtubules (MT) are dynamically instable, assembling and disassembling structures of the cell. Tubulin, the major building protein of MT, is a heterodimer consisting of α and ẞ subunits. Agents that bind to tubulin and inhibit its assembly lead to the inhibition of MT formation. Such tubulin-binding agents are usually termed MT-disassembling agents or antitubulins. Endocytosis, matrix protein secretion, cell division, cell migration and inflammation are examples of MT-dependent processes. Their dysfunction, in particular in arterial smooth muscle cells (ASMC), is critically involved in atherogenesis. Here we Dance round (i) MT-based secretory pathway in ASMC and, in turn, antitubulins for atherosclerosis therapy, and (ii) the neurotrophins, particularly nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) and their receptors Trk (tyrosine receptor kinase; pronounced “track”), introducing the term trackins – Trk-targeting agents (TTA) that influence positively (agonistically) or negatively (antagonistically) the activity of TrkA receptor for NGF and/or TrkB receptor for BDNF. We propose that some trackins and their native ligands may have therapeutic potentials for cardiometabolic, neuropsychiatric, oncologic and other diseases. Finally the interaction of MT-tubulin and neurotrophin Trk receptors is outlined.