Brain-derived neurotrophic factor as a prototype neuroprotective factor against HIV-1-associated neuronal degeneration.
Patients with human immunodeficiency virus type 1 (HIV-1) infection develop a broad spectrum of motor impairments and cognitive deficits, which follow or parallel cellular loss and atrophy in their brains. The viral envelope glycoprotein 120 (gp120) has been suggested to be a causal agent of neuronal loss. Therefore, reducing gp120 neurotoxicity may prevent neuronal degeneration seen in these patients. Here, we describe in vitro and in vivo experimental evidence that gp120 toxicity can be reduced by brain-derived neurotrophic factor (BDNF), a naturally occurring peptide that has been shown to block neurotoxin and trauma-induced neuronal injury. Moreover, we review the survival promoting properties of BDNF and the issues concerning its delivery into the brain, in an attempt to explain the rationale for exploring BDNF as a prototype trophic factor for a therapy to reduce neuronal cell death in HIV-1 infected patients.
Nosheny
R L
RL
Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA.
Mocchetti
I
I
Bachis
A
A
D015526:AIDS Dementia Complex / Q000188:drug therapy* / Q000473:pathology*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology; D015497:HIV-1; D006801:Humans; D009414:Nerve Growth Factors / Q000502:physiology; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000473:pathology*; D009474:Neurons / Q000473:pathology*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D020258:Neurotoxicity Syndromes / Q000378:metabolism / Q000473:pathology; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D020917:Receptor, trkA / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D015699:HIV Envelope Protein gp120; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA