HDGF2 (Cryptic Specific) Antibody #95895

Hepatoma-derived growth factor-related protein 2 (HDGF2), encoded by the gene HDGFL2, is a ubiquitously expressed histone-binding protein belonging to the larger family of hepatoma-derived growth factor (HDGF) and HDGF-related proteins (HRPs). Structurally, HDGF2 and its family members share a highly conserved amino terminus region, termed homologous to the amino terminus of HDGF (HATH). Contained within the HATH region is a Pro-Trp-Trp-Pro (PWWP) domain, which recognizes and binds histone H3 lysine 36 di- and trimethylation. HDGF2 functions through this domain to regulate chromatin structure and DNA repair (1-3).

Exon splicing of HDGF2 mRNA is regulated by TAR DNA-binding protein 43 (TDP43), a ubiquitously expressed DNA/RNA-binding protein belonging to the heterogeneous nuclear ribonucleoprotein (hnRNP) family. Dysfunctional TDP43, driven by genetic mutations, hyperphosphorylation, ubiquitination, and cleavage forms insoluble cytoplasmic aggregates. These aggregates are pathological hallmarks of patients with amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), and limbic predominant age-related TDP-43 encephalopathy (LATE). These inclusions are also present in some patients with other neurodegenerative diseases (NDDs), including Alzheimer’s disease (AD) and Chronic traumatic encephalopathy (CTE) (4,5). TDP43 cytoplasmic mislocalization and aggregation lead to altered HDGF2 mRNA splicing and the inclusion of cryptic exons. This results in an alternative translated HDGF2 protein that includes cryptic exon-encoded neo epitopes. Neo epitope-containing HDGF2 is detected in CSF and plasma, suggesting it may be a biomarker for neurodegenerative diseases with TDP43 pathology (6,7).