Cytoplasmic dynein 1 heavy chain 1

Cytoplasmic dynein 1 heavy chain 1 (DYNC1H1) is a large molecular motor protein that drives retrograde intracellular transport of vesicles and organelles along microtubules through ATP hydrolysis. It also functions in mitotic spindle assembly and metaphase plate congression (UniProt: Q14204).

DYNC1H1 is widely expressed and mutations have been associated with several neurological disorders, including Charcot-Marie-Tooth disease type 2O (CMT2O), cortical dysplasia with brain malformations (CDCBM13), and spinal muscular atrophy lower extremity-predominant 1 (SMALED1) (UniProt: Q14204). These associations highlight its critical role in neuronal function and development.

In Alzheimer's disease, DYNC1H1 is significantly downregulated in post-mortem brain tissue relative to age-matched controls. Across two subcellular fractions examined in TMT-labeled proteomics experiments, the protein showed a mean log2 fold-change of −0.37 (Chaparral AD proteomics). This downregulation may reflect impaired axonal transport machinery in AD pathology.