Microtubuledestabilizing

Microtubules are dynamic, tubular polymers of alpha- and beta-tubulin that form part of the cytoskeleton in eukaryotic cells. They measure about 25 nanometers in diameter and assemble into filamentous networks that provide structural support, organize intracellular transport, and form the mitotic spindle during cell division.

Structure and dynamics: Polarized ends, plus end grows and minus end shrinks; GTP binding and hydrolysis drive dynamic instability; nucleated by gamma-tubulin ring complexes at microtubule organizing centers such as the centrosome; stabilizing or destabilizing microtubules through associated proteins and post-translational modifications.

Clinical relevance: Genetic disorders called tubulinopathies arise from mutations in tubulin genes (e.g., TUBA1A, TUBB2B, TUBB3) and disrupt brain development, leading to cortical malformations such as lissencephaly, pachygyria, or simplified gyral patterns. Other diseases involve microtubule-associated proteins (MAPs) and tau; tau pathology (NFTs) is a hallmark of Alzheimer’s disease and related dementias.

In cancer, microtubules are targets of chemotherapy: taxanes stabilize microtubules (paclitaxel, docetaxel) while vinca alkaloids destabilize them (vincristine, vinblastine), interrupting mitosis but causing neuropathy, myelosuppression, and other adverse effects; resistance mechanisms include tubulin mutations and efflux pumps.

Research and diagnostics: Advances in cryo-electron microscopy reveal microtubule architecture; tubulin isotype diversity affects drug sensitivity; ongoing work aims to map tubulin gene variants to neurodevelopmental phenotypes and to develop targeted therapies with fewer side effects.