Tubulin beta-3 chain

Tubulin beta-3 chain (TUBB3) is a core component of microtubules, the polymeric protein filaments essential for cellular architecture and dynamics (UniProt: Q13509). TUBB3 heterodimerizes with alpha-tubulin and polymerizes via GTP-driven addition to microtubule ends. The protein plays a critical role in axon guidance and maintenance, including dorsal root ganglion axon projection toward the spinal cord, with netrin-1 signaling modulating microtubule dynamics through TUBB3-containing structures.

UniProt associates TUBB3 with two primarily neurodevelopmental diseases: congenital fibrosis of extraocular muscles type 3A (CFEOM3A) and cortical dysplasia with brain malformations (CDCBM1), both reflecting its essential role in neuronal migration and axonal organization.

In Alzheimer's disease, TUBB3 is downregulated in post-mortem AD brain tissue relative to age-matched controls, with a mean log2 fold-change of −0.41 across three subcellular fractions (Chaparral AD proteomics). This reduction may reflect impaired microtubule dynamics and axonal integrity associated with neurodegeneration in AD pathology.