PMID- 15581399
OWN - NLM
STAT- MEDLINE
DCOM- 20050105
LR  - 20191109
IS  - 0892-0915 (Print)
IS  - 0892-0915 (Linking)
VI  - 16
IP  - 1-2
DP  - 2004
TI  - Brain-derived neurotrophic factor activation of TrkB protects neurons from 
      HIV-1/gp120-induced cell death.
PG  - 51-7
AB  - 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.
FAU - Mocchetti, Italo
AU  - Mocchetti I
AD  - Department of Neuroscience, Georgetown University Medical Center, Washington DC 
      20057, USA. moccheti@georgetown.edu
FAU - Bachis, Alessia
AU  - Bachis A
LA  - eng
GR  - NS040670/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - United States
TA  - Crit Rev Neurobiol
JT  - Critical reviews in neurobiology
JID - 8710803
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (HIV Envelope Protein gp120)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.4.22.- (CASP3 protein, human)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects/physiology
MH  - Brain-Derived Neurotrophic Factor/*physiology
MH  - Caspase 3
MH  - Caspases/physiology
MH  - Cell Death/drug effects
MH  - Gene Expression Regulation/physiology
MH  - HIV Envelope Protein gp120/*toxicity
MH  - Humans
MH  - Mitogen-Activated Protein Kinases/physiology
MH  - Neurons/pathology/*physiology
MH  - Receptor, trkB/*genetics
RF  - 38
EDAT- 2004/12/08 09:00
MHDA- 2005/01/06 09:00
CRDT- 2004/12/08 09:00
PHST- 2004/12/08 09:00 [pubmed]
PHST- 2005/01/06 09:00 [medline]
PHST- 2004/12/08 09:00 [entrez]
AID - 54f83f6510f9db32,2c9bc8cc1b8128f0 [pii]
AID - 10.1615/critrevneurobiol.v16.i12.50 [doi]
PST - ppublish
SO  - Crit Rev Neurobiol. 2004;16(1-2):51-7. doi: 10.1615/critrevneurobiol.v16.i12.50.