%0 Journal Article
%T Amelioration of caspase 3,7 activity by SP01 in human primary neurons exposed to HIV
%A Amol Shah
%A Gursharan Chana
%A Ginger R Lucero
%A et al
%J Neurobehavioral HIV Medicine
%D 2010
%I 
%R http://dx.doi.org/10.2147/NBHIV.S8711
%X melioration of caspase 3,7 activity by SP01 in human primary neurons exposed to HIV Rapid Communication (2642) Total Article Views Authors: Amol Shah, Gursharan Chana, Ginger R Lucero, et al Published Date July 2010 Volume 2010:2 Pages 33 - 37 DOI: http://dx.doi.org/10.2147/NBHIV.S8711 Amol Shah1, Gursharan Chana1,2, Ginger R Lucero1, Eliezer Masliah3, Cristian L Achim1, Laurent Lecanu4, Vassilios Papadopoulos4, Janet Greeson5, Ian P Everall1,2 1Department of Psychiatry, HIV Neurobehavioral Research Center, University of California, San Diego, School of Medicine, La Jolla, CA, 92093, USA; 2Department of Psychiatry, The University of Melbourne, Royal Melbourne Hospital, VIC, 3050, Australia; 3Department of Neurosciences, University of California, San Diego, School of Medicine, La Jolla, CA, 92093, USA; 4The Research Institute of the McGill University Health Centre and Department of Medicine, McGill University, Montreal QC, Canada; 5Samaritan Pharmaceuticals, Las Vegas, Nevada Abstract: Despite development of antiretroviral therapy (ARV) HIV associated neurocognitive disorder (HAND) continues to be a significant cause of morbidity. As ARVs are not entirely effective against HAND, there is significant motivation to discover novel therapies that are targeted towards the treatment of HAND. A novel formulation of procaine hydrochloride, SP01, is one potential molecule which has shown promise. Phase I clinical trials have found SP01 treatment to significantly increase CD4 cell counts and quality of life parameters in HIV infected patients. To assess SP01¡¯s potential use for HAND we utilized an in vitro human -primary neuron culture model and conducted co-exposure experiments with gp120 ([BaL] 300 pg/mL) or HIV (BaL) 500 pg/mL) with or without SP01 (10 ¦ÌM) and measured the activity of the pro-apoptotic caspases 3/7 using a quantitative luminescence assay. Both gp120 and HIV resulted insignificant increase in caspase 3/7 activity from controls (P < 0.05). This effect was ameliorated with co-exposure with SP01 (P < 0.05). The reduction in activity of caspases 3 and 7, which are well known to be cellular triggers for apoptosis, signifies that SP01 is likely to have neuroprotective effects against HIV induced neurodegeneration via inhibition of pro-apoptotic cascades. Given its success in clinical trials and in vitro experiments, SP01 seems to be a legitimate contender in the fight against HAND.
%K HIV
%K SP01
%K neurotoxicity
%K caspase
%K HAND
%K neuroprotection
%U https://www.dovepress.com/amelioration-of-caspase-37-activity-by-sp01-in-human-primary-neurons-e-peer-reviewed-article-NBHIV