Emerging neuromodulatory molecules for the treatment of neurogenic erectile dysfunction caused by cavernous nerve injury.
Advances in the neurobiology of growth factors, neural development, and prevention of cell death have resulted in a heightened clinical interest for the development of protective and regenerative neuromodulatory strategies for the cavernous nerves (CNs), as therapies for prostate cancer and other pelvic malignancies often result in neuronal damage and debilitating loss of sexual function. Nitric oxide released from the axonal end plates of these nerves within the corpora cavernosa causes relaxation of smooth muscle, initiating the haemodynamic changes of penile erection as well as contributing to maintained tumescence; the loss of CN function is primarily responsible for the development of erectile dysfunction (ED) after pelvic surgery and serves as the primary target for potential neuroprotective or regenerative strategies. Evidence from pre-clinical studies for select neuromodulatory approaches is reviewed, including neurotrophins, glial cell line-derived neurotrophic factors (GDNF), bone morphogenic proteins, immunophilin ligands, erythropoetin (EPO), and stem cells.
Bella
Anthony J
AJ
The Ottawa Hospital, Civic Campus, B3-Division of Urology, Ottawa K1Y 4E9, Canada. anthonybella@gmail.com
Lin
Guiting
G
Cagiannos
Ilias
I
Lue
Tom F
TF
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000627:therapeutic use; D019208:Brain-Derived Neurotrophic Factor / Q000627:therapeutic use; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000209:etiology* / Q000628:therapy; D004921:Erythropoietin / Q000627:therapeutic use; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000627:therapeutic use; D055428:Growth Differentiation Factor 5; D006801:Humans; D020104:Immunophilins; D008297:Male; D009414:Nerve Growth Factors / Q000627:therapeutic use; D018377:Neurotransmitter Agents / Q000627:therapeutic use*; D010413:Penis / Q000294:innervation*; D059348:Peripheral Nerve Injuries; D011183:Postoperative Complications; D033581:Stem Cell Transplantation
D019485:Bone Morphogenetic Proteins; D019208:Brain-Derived Neurotrophic Factor; C525893:GDF5 protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D055428:Growth Differentiation Factor 5; D009414:Nerve Growth Factors; D018377:Neurotransmitter Agents; D004921:Erythropoietin; D020104:Immunophilins