Tubulin beta-8 chain

Tubulin beta-8 chain (TUBB8) is a structural protein and major component of microtubules, which are cylindrical assemblies of alpha- and beta-tubulin heterodimers (UniProt: Q3ZCM7). The protein plays a critical role in microtubule dynamics by facilitating GTP-dependent polymerization at microtubule ends and subsequent GTP hydrolysis to GDP-bound tubulin. TUBB8 has specialized functions in meiotic spindle assembly and oocyte maturation, with mutations linked to oocyte/zygote/embryo maturation arrest (OZEMA2), a primary infertility disorder characterized by metaphase I arrest (UniProt: Q3ZCM7).

In Alzheimer's disease, TUBB8 is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls (mean log2 fold-change: −0.62; Chaparral AD proteomics). This reduction was detected in TMT-labeled quantitative proteomics of subcellular fractions from human AD brain tissue. Decreased tubulin levels may reflect compromised microtubule stability and axonal integrity, processes implicated in neurodegeneration, though the functional consequences of reduced TUBB8 specifically in AD pathogenesis remain to be elucidated.