Probable ATP-dependent RNA helicase DDX5

DDX5 (P17844) is a probable ATP-dependent RNA helicase with diverse molecular functions spanning RNA processing and transcriptional regulation (UniProt: P17844). Its RNA helicase activity regulates alternative splicing of tau pre-mRNA in an RBM4-dependent manner by binding to stem-loop regions downstream of exon 10. Beyond RNA metabolism, DDX5 serves as a transcriptional coactivator for multiple factors including androgen receptor, p53/TP53, RUNX2, and MYOD1, and acts in circadian rhythm control as part of the PER complex.

DDX5 has been implicated in neurodegenerative processes given its role in tau splicing regulation, a pathway central to Alzheimer's pathology. The protein is involved in transcriptional responses to DNA damage and p53-dependent apoptosis, processes relevant to neuronal stress (UniProt: P17844).

DDX5 is significantly down-regulated in Alzheimer's disease brain tissue compared to age-matched controls, with a mean log2 fold-change of −1.73 across post-mortem AD samples analyzed by TMT-labeled proteomics in four subcellular fractions (Chaparral AD proteomics). This downregulation may impair tau splicing regulation and transcriptional stress responses, potentially contributing to AD pathogenesis.