Caspase inhibitors treatment

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. 

Studies Showing the Effect of Treatment with Caspase Inhibitors in Experimental Models of Ischemia/Reperfusion Injury to the Heart0... 

Linton SD, et al. Eirst-in-class pan caspase inhibitor developed for the treatment of liver disease. J. Med. Chem. 2005 48 6779-6782. 

Diverse drug targets in this field are at an early stage of development, such as endogenous inhibitors of apoptosis proteins (lAP), a family of caspase inhibitors that selectively bind and inhibit caspases-3, -7, and -9. The inhibition of these lAP might stimulate apoptosis of cancer cells with potential as a treatment of malignancy. ... 

Cell death by apoptosis, a phenomenon that is increasingly considered the ultimate cause of many diseases, is also one of the patent toxic manifestations of okadaic acid. Micromorphological studies have demonstrated a parallel between the hyperphosphorylation of neuronal cytoskeletal proteins in Alzheimer disease and that produced by a treatment of cultured rat neurones with okadaic acid, which is accompanied by rounding of the cellular bodies and neurite degeneration. DNA fragmentation and neuronal death are inhibited by the presence of cycloheximide and by the caspase inhibitor benzoyloxycarbonyl-Val-Ala-Asp-O-methoxy-fluoromethyl ketone (ZVAD) [134, 135], Okadaic acid was reported to be an apoptopic agent in rat thymocytes, because it causes... 

J. I Matsui, A. Haque, D. Huss, E. P. Messana, J. A. Alosi, J. W. Roberson, D. A. Cotanche, J. D. Dickman, and M. E. Warchol, Caspase inhibitors promote vestibular hair cell survival and function after aminoglycoside treatment in vivo, J. Neurosci, 23 (2003) 6111-6122. 

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. 

Constitutive activation of the P13-K - Akt/PKB survival signaling pathway is a likely mechanism by which many cancers become refractory to cytotoxic therapy. In LNCaP prostate cancer cells, the PTEN is inactivated, leading to constitutive activation of Akt/PKB and resistance to apoptosis. However, apoptosis and inactivation of Akt/PKB can be induced in these cells by treatment with P13-K inhibitors. Surprisingly, androgen, epidermal growth factor, or semm can protect these cells from apoptosis, even in the presence of P13-K inhibitors and without activation of Akt/PKB, indicating the activity of a novel, Akt/PKB-independent survival pathway. This pathway blocks apoptosis at a level prior to caspase 3 activation and release of cytochrome c from mitochondria (Carson et al, 1999)... 

The TNF-a-induced DNA fragmentation may have been caused by caspase-activated deoxyribonuclease (CAD) in PC-12 cells. In non-apoptotic cells, CAD is present as an inactive complex with the inhibitor jOvd p3,24]. During apoptosis, caspase-3 inactivates ICAD, leaving CAD free to function as a nuclease [25]. Therefore, we used die fluorogenic substrate, Ac-DEVD-MCA, to determine whether the caspase-3 in PC-12 cells was activated by treatment with TNF-a and/or crocin. As shown in... 

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