Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neurons are targets of toxicity induced by the human immunodeficiency virus (HIV)-1 protein Tat (transactivator of transcription). Exposure to Tat increases [Ca(2+)](i) in striatal neurons and activates multiple cell death pathways. In earlier studies the authors showed that Tat activated both caspase-3 and endonuclease-G, a caspase-independent effector of apoptosis, and that Tat-induced neurotoxicity was not attenuated by a caspase-3 inhibitor. Because Tat activates multiple, parallel death pathways, the authors attempted to reduce Tat-induced neurotoxicity by manipulating signaling pathways upstream of mitochondrial apoptotic events. PTEN (phosphatase and tensin homolog deleted on chromosome 10), a negative regulator of Akt/PKB (protein kinase B) phosphorylation, was chosen as a target for silencing. Akt/PKB activity directs multiple downstream pathways mediated by GSK3beta, BAD, forkhead transcription factors, nuclear factor kappa B (NFkappaB), and others, in a manner that promotes proliferation and survival. Striatal neurons were nucleofected with short interfering RNA (siRNA) vectors targeting PTEN, or a negative-control siRNA. Although Tat(1-86) significantly increased the death of neurons transfected with control construct by 72 h, PTEN-silenced neurons were completely protected. These findings indicate that Akt is a critical intermediary in the direct neurotoxicity induced by HIV-1 Tat, and identify Akt regulation as a possible therapeutic strategy for Tat-induced neurotoxicity in HIV encephalitis (HIVE).
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PMID:Silencing the PTEN gene is protective against neuronal death induced by human immunodeficiency virus type 1 Tat. 1750 78

There is increasing concern that HIV treatment failure may result from inadequate central nervous system (CNS) penetration of antiretroviral drugs, allowing compartmentalized viral replication and development of resistance. We discuss a patient who maintained a suppressed plasma viral load for four years on antiretroviral therapy (ART) before developing HIV encephalitis with a cerebrospinal fluid (CSF) HIV viral load of 861 copies/mL and newly detectable plasma viral load of 68 copies/mL. Identification of major resistance mutations to his combination therapy supported concerns that resistant HIV had developed within the CNS. His ART was changed to optimize CNS penetration, leading to maintained clinical improvement. Imaging presented demonstrates corresponding radiological improvement. The report illustrates the need to exclude CNS viral rebound or incomplete suppression in HIV patients with neurological symptoms, and suggests that the extent of this emerging problem is only beginning to be recognized as the implications of long-term peripheral HIV suppression unfold.
Int J STD AIDS 2011 Oct
PMID:HIV encephalitis despite suppressed viraemia: a case of compartmentalized viral escape. 2199 85

We report a case of primary HIV encephalitis, which initially presented as acute psychosis. Magnetic resonance imaging of the brain was suggestive of vasculitis and multiple infarctions, whereas a brain biopsy after six weeks of symptoms showed HIV encephalitis with microglial nodules, but no signs of vasculitis. We review previous reported cases and radiological findings in HIV encephalitis and discuss the role of antiretroviral therapy and steroids in its management.
Int J STD AIDS 2013 Jun
PMID:Encephalitis in primary HIV infection: challenges in diagnosis and treatment. 2397 Jul 54

We report an unusual case of human immunodeficiency virus (HIV) infection initially presenting with hypothermia and bradycardia associated with an HIV encephalitis. Searches reveal only five reported cases of spontaneous episodic hypothermia in the context of HIV infection. In our case, magnetic resonance imaging revealed the presence of a persistent cavum septum pellucidum (CSP), an anatomical and functional neuro-developmental abnormality, as well as changes compatible with an HIV encephalitis. Episodic hypothermia can occur in association with agenesis of the corpus callosum, known as Shapiro's syndrome, and the presence of a persistent CSP in our case suggests it may have contributed to the clinical presentation.
Int J STD AIDS 2020 Oct
PMID:Hypothermia - an unusual initial presentation of human immunodeficiency virus infection. 3275 14