rol de de las immunophilinas en la recuperacion de la funcion erectil luego de la injuria del nervio cavernoso

1: J Sex Med. 2009 Mar;6 Suppl 3:340-6. Links

Role of immunophilins in recovery of erectile function after cavernous nerve injury.

Sezen SF, Lagoda G, Burnett AL.

James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Department of Urology, Baltimore, MD 21287, USA. ssezen1@jhmi.edu

INTRODUCTION: Immunophilin ligands provide potentially new alternatives for the treatment of erectile dysfunction (ED), which occurs after injury of the cavernous nerves (CNs). AIM: To review and update current knowledge of the neurotrophic effects and likely mechanism of action of immunophilin proteins with emphasis on the FK506-binding protein (FKBP) subfamily and the role of immunophilin ligands for the treatment of CN injury-induced ED. METHODS: Review of available reports of studies investigating the effects and neurotrophic mechanisms of immunophilin ligands involved in erectile function recovery in rodent models of CN injury. MAIN OUTCOME MEASURES: Erection parameters and molecular correlations associated with CN injury and functional recovery. RESULTS: Treatment with prototype immunosuppressive immunophilin ligands FK506 (FK) and rapamycin (Rapa) improve erectile function in animal models of CN injury. Similarly, non-immunosuppressive analogs such as GPI-1046 and FK1706 are effective in recovery of erections after CN injury. Neuronal nitric oxide may influence the erection recovery effects of immunophilin ligands after CN injury. FKBPs 38 and 65 expression changes in the penis and its innervation coincide with the neurotrophic effects of immunophilin ligands. Antioxidative actions of immunophilin ligands contribute to their neurotrophic effects. Immunophilins are localized to nerves coursing in human prostate and penile tissue. CONCLUSIONS: The findings support the hypothesis that immunophilin ligands, working through specific receptor mechanisms that are specific to injured CN, are potentially useful to sustain erectile function in men following radical prostatectomy.

PMID: 19267858 [PubMed - indexed for MEDLINE]

Modulacion del factor de crecimiento en respuesta a las injurias del nervio cavernosos

1: J Sex Med. 2009 Mar;6 Suppl 3:347-52. Links

Nerve growth factor modulation of the cavernous nerve response to injury.

Bella AJ, Lin G, Lin CS, Hickling DR, Morash C, Lue TF.

Division of Urology, Department of Surgery, University of Ottawa, Ottawa, Canada. abella@ohri.ca

INTRODUCTION: Surgical therapies for prostate cancer and other pelvic malignancies often result in neuronal damage and debilitating loss of sexual function due to cavernous nerve (CN) trauma. Advances in the neurobiology of growth factors have heightened clinical interest in the development of protective and regenerative neuromodulatory strategies targeting CN recovery following injury. AIM: The aim of this review was to offer an examination of current and future nerve growth factor (NGF) modulation of the CN response to injury with a focus on brain-derived nerve growth factor (BDNF), growth differentiation factor-5 (GDF-5), and neurturin (NTN). METHODS: Information for this presentation was derived from a current literature search using the National Library of Medicine PubMed Services producing publications relevant to this topic. Search terms included neuroprotection, nerve regeneration, NGFs, neurotrophic factors, BDNF, GDF-5, NTN, and CNs. MAIN OUTCOME MEASURES: Basic science studies satisfying the search inclusion criteria were reviewed. RESULTS: In this session, BDNF, atypical growth factors GDF-5 and NTN, and their potential influence upon CN recovery after injury are reviewed, as are the molecular pathways by which their influence is exerted. CONCLUSIONS: Compromised CN function is a significant cause of erectile dysfunction development following prostatectomy and serves as the primary target for potential neuroprotective or regenerative strategies utilizing NGFs such as BDNF, GDF-5, and NTN, and/or targeted novel therapeutics modulating signaling pathways.

PMID: 19267859 [PubMed - indexed for MEDLINE]

PMCID: PMC2706280