Table 2. Preclinical protein therapy on ED biotherapeutics.
| Protein type | Protein names | Type of ED | Target signaling | Reference |
|---|---|---|---|---|
| Recombinant protein | HEBP1 | Type 1 diabetic ED | Angiogenesis, ROS, PI3K/AKT/eNOS | [28] |
| Recombinant protein | VEGF | Vasculogenic ED, age-associated ED, CNI-ED | Angiogenesis, smooth muscle integrity | [37,38,39] |
| Recombinant protein | Angiopoietin-1 | Type 2 diabetic ED | Angiogenesis, eNOS phosphorylation | [40] |
| Recombinant protein | COMP-angiopoietin-1 | Type 1 diabetic ED, high-cholesterol ED | Angiogenesis, NO-cGMP, ROS, tight junction | [41,42] |
| Recombinant protein | Angiopoietin-4 | Type 1 diabetic ED | Angiogenesis, Tie2, eNOS phosphorylation | [43] |
| Recombinant protein | HGF | Type 1 diabetic ED | Angiogenesis, ROS, smooth muscle integrity | [44,45] |
| Recombinant protein | Sonic hedgehog | CNI-ED, age-associated ED | Nerve regeneration, neurotrophic factors | [46,47,48] |
| Recombinant protein | DKK2 | Type 1 diabetic ED, CNI-ED | Angiogenesis, nerve regeneration, Ang1-Tie2, eNOS phosphorylation, ROS, neurotrophic factors | [49,50] |
| Recombinant protein | Apelin | Type 1 diabetic ED, CNI-ED | Angiogenesis, NO-cGMP, ROS | [51] |
| Recombinant protein | LRG1 | Type 1 diabetic ED | Angiogenesis, nerve regeneration, tight junction, eNOS phosphorylation, ROS, PI3K/AKT/NFkB | [52] |
| Recombinant protein | BDNF | CNI-ED, age-associated ED | Angiogenesis, nerve regeneration, nNOS, cGMP | [37,53] |
| Monoclonal antibody | TrkA | CNI-ED | Nerve regeneration, nNOS, smooth muscle integrity | [54] |
| Monoclonal antibody | Ninjurin 1 | Type 1 diabetic ED, CNI-ED | Angiogenesis, Ang1-Tie2, eNOS phosphorylation, ROS, neurotrophic factors | [55,56] |
| Polyclonal antibody | proNGF | CNI-ED | Angiogenesis, nerve regeneration, nNOS, eNOS phosphorylation cGMP | [57] |
ED, erectile dysfunction; VEGF, vascular endothelial growth factor; COMP, cartilage oligomeric matrix protein; HGF, hepatocyte growth factor; BDNF, brain-derived neurotrophic factor; DKK2, dickkopf WNT signaling pathway inhibitor 2; HEBP1, heme-binding protein 1; LRG1, leucine-rich alpha-2-glycoprotein 1; TrkA, tyrosine receptor kinases; proNGF, precursor for nerve growth factor; CNI, cavernous nerve injury; eNOS, endothelial nitric oxide synthase; NO, nitric oxide; cGMP, cyclic guanosine monophosphate; ROS, reactive oxygen species; PI3K, phosphoinositide 3-kinase; AKT, protein kinase B; NFkB, Nuclear factor kappa B; nNOS, neuronal nitric oxide synthase.