Caspases anti treatment

Other potential approaches involve the use of anti-apoptotic treatments, such as caspase-1 inhibitors or HDAC inhibitors which may interfere with the transcriptional dysregulation seen in Huntington disease. Both approaches have resulted in encouraging results in animal experiments. The use of growth factors has also been suggested as possible treatment for Huntington s disease. 

Investigational agents for the treatment of HCV infection are multiple and include inhibitors of the HCV RNA polymerase such as valopicitabine. Pis such as telaprevir, the ribavirin analogs merimepodib and viramidine, an anti-aminophospholipid antibody, a caspase inhibitor, and the immunomodulator thymosin alpha-1. 

Oxidative stress appears to have a central role in the induction of apoptosis following the exposure of cells to a range of cytotoxic insults. Anti-apoptotic properties of the antioxidant, 4b,5,9b,10-tetrahydroindeno[l,2-b]indole, in Jurkat T cells subjected to a number of cytotoxic insults. Peroxide and superoxide anion production following UV treatment showed that indole derivative was found to only partially inhibit superoxide anion production and exhibited strong inhibition of caspase-3 activation in UV [115]. 

In vivo neuroprotection by HDAC inhibition has been linked to upregulation of transcription of antioxidant and growth factor proteins, stimulation of neurogenesis [255], and anti-inflammatory effects [256-258]. An anti-inflammatory effect has been achieved by suppression of microglial activation [259], inhibition of pro-inflammatory cytokine expression [260], or NFkB-mediated inflammatory responses. Treatment with HDAC inhibitors also markedly inhibited ischemia-induced p53 overexpression [261, 262]. In an animal model of multiple sclerosis (experimental autoimmune encephalomyelitis, EAE), treatment with TSA (2, Fig. 1) activated a transcriptional program that culminated in decreased caspase 3 activity [263]. In HD, treatment of Drosophila mutants expressing Htt with the HDAC inhibitors SAHA or TSA (1 or 2, Fig. 1) suppressed neuronal photoreceptor generation [177]. 

Many quinazolinone-based compounds function as thymidylate synthase inhibitors by directly binding to the active site of thymidylate synthase. This results in the inhibition of DNA replication as well as DNA damage, S-phase cell arrest, and caspase-dependent apoptosis. Many compounds of this class have been successfully employed as anti-cancer pharmaceutics. Two examples, nolatrexed, a compound used to treat unresectable hepatocellular carcinoma (HCC), and raltitrexed, a first-line treatment against advanced colorectal cancer, are highlighted below. 

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