Peripheral benzodiazepines receptor (PBR) stimulates steroidogenesis: A potential neuroprotective pathway following brain damage
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1
Pontificia Universidad Javeriana, Colombia
The effects of neuroactive steroids have been highly assessed for their significance on inflammation resolution induced by cytotoxic agents. Steroids are derived from cholesterol, and this regulatory pathway may be a target for possible protective strategies. For example, the increased expression of peripheral benzodiazepine receptor (PBR) stimulates steroids production, and the action of specific ligands on PBR favors the reduction of glial activity and act as a protective mechanism. The augmented expression of PBR and steroidogenic acute regulatory protein (StAR) after injury is associated with local production of steroids by glial cells. For instance, cholesterol is captured by StAR in the outer mitochondrial membrane that transfers it to PBR, which uses it as substrate for the enzyme P450scc in the inner mitochondrial membrane. Some ligands, such as 4'-Chlorodiazepam (Ro5-4864) and isoquinoline carboxamide (PK 11195), act as agonists of the PBR receptor. Previous studies indicate that Ro5-4864 reduces neuronal loss, thus implying the regulation of mitochondrial transition after a traumatic brain injury. In this work, we assess the effects of PBR ligands directly involved in neuronal cell survival and proliferation after injury, thereby activating potential downstream targets as novel therapeutic approaches.
References
Barreto GE, Santos-Galindo M, Garcia-Segura LM. Selective estrogen receptor modulators regulate reactive microglia after penetrating brain injury. Front Aging Neurosci, 6:132, 2014.
Avila-Rodriguez M, Garcia-Segura LM, Cabezas R, Torrente D, Capani F, Gonzalez J, Barreto GE. Tibolone protects T98G cells from glucose deprivation. J Steroid Biochem Mol Biol., 2014, In Press.
Barreto G , Santos-Galindo M, Diz-Cháves Y, Pernía O, Carrero P, Azcoitia I, Garcia-Segura LM. Selective Estrogen Receptor Modulators decrease reactive astrogliosis in the injured brain: Effects of aging and prolonged depletion of ovarian hormones. Endocrinology 150(11):5010-5, 2009.
Keywords:
Peripheral benzodiazepine receptor,
ligands,
Inflammation,
Brain Injury,
Neuroprotection
Conference:
Latin-American School on glial cells in the diseased brain (IBRO), Bogotá, Colombia, 13 Jul - 17 Jul, 2015.
Presentation Type:
Poster Presentation
Topic:
Traumatic and Cerebrovascular diseases
Citation:
Hidalgo Lanussa
OA,
Ávila-Rodriguez
M and
Barreto
G
(2015). Peripheral benzodiazepines receptor (PBR) stimulates steroidogenesis: A potential neuroprotective pathway following brain damage.
Conference Abstract:
Latin-American School on glial cells in the diseased brain (IBRO).
doi: 10.3389/conf.fncel.2015.35.00003
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Received:
23 Feb 2015;
Published Online:
16 May 2015.
*
Correspondence:
Prof. George E. Barreto, Pontificia Universidad Javeriana, Bogotá, Colombia, gesbarreto@gmail.com