Alpha-internexin

Alpha-internexin (INA) is a Class-IV neuronal intermediate filament protein that plays a key role in neuron morphogenesis (UniProt: Q16352). It can self-assemble into independent filamentous networks or cooperate with other neurofilament proteins—particularly NEFL—to form the structural backbone of the neuronal cytoskeleton, with NEFM and NEFH attaching as cross-bridges. This protein is primarily expressed in neuronal tissues where it contributes to cytoskeletal integrity and neuronal architecture.

Alpha-internexin has been identified as relevant to Alzheimer's Disease pathology. Chaparral AD proteomics data from human post-mortem AD brain tissue (TMT-labeled DDA analysis across four subcellular fractions) show that alpha-internexin is significantly downregulated in AD compared to age-matched controls, with a mean log2 fold-change of −0.40. This reduction in expression may reflect cytoskeletal disruption or neuronal degeneration associated with AD pathology. The downregulation across the analyzed fractions suggests a broad decrease in this structural protein in diseased tissue.