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Critical Reviews™ in Neurobiology
SJR: 0.121

ISSN Imprimir: 0892-0915
ISSN On-line: 2375-0014

Archives: Volume 10, 1996 to Volume 20, 2008

Critical Reviews™ in Neurobiology

DOI: 10.1615/CritRevNeurobiol.v16.i12.50
pages 51-58

Brain-Derived Neurotrophic Factor Activation of TrkB Protects Neurons from HIV-1/gp120-Induced Cell Death

Italo Mocchetti
Department of Neuroscience, Georgetown University Medical Center, Washington DC, USA
Alessia Bachis
Department of Neuroscience, Georgetown University Medical Center, Washington DC, USA

RESUMO

Patients with the human immunodeficiency virus type 1 (HIV-1) develop in the late phase of infection a complex of neurological signs termed Acquired Immune Deficiency Syndrome-Related Dementia (ADC). These patients exhibit cortical and subcortical atrophy. Considerable experimental data indicate that the HIV-1 envelope glycoprotein gp120 may be one of the agents causing neuronal cell death. Gp120 causes neuronal cell death both in vitro and in vivo by activating a caspase-dependent apoptotic pathway, and in particular caspase-3. The neurotrophin brain-derived neurotrophic factor (BDNF) has been shown to prevent gp120-mediated apoptosis of cerebellar granule cells by inhibiting caspase-3 activation. However, the signal transduction pathway that contributes to the neuroprotective effects of BDNF has not been determined. BDNF binds with high affinity to the tyrosine kinase receptor TrkB and activates different intracellular signaling cascade including the extracellular signal-related kinases (ERK) and the phosphatidylinositol 3-kinase (PI3-K). Pharmacological inhibition of TrkB or ERK1/2, but not PI3-K, greatly reduced the ability of BDNF to block gp120-mediated apoptosis of cerebellar granule cells. These findings suggest that TrkB-mediated activation of ERK1/2 is the main signaling pathway that contributes to neuroprotection against gp120.


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