In vivo results in various animal models are very consistent, showing that the CASP6 inhibition by Z-VEID-FMK (a specific CASP6 inhibitor) or deletion can attenuate inflammatory and neuropathic pain (Berta 2014, 2016).
Impairment of spinal TNF-[alpha] was also observed in mice with CASP6 deficiency compared to their wild-type controls after tissue injury and damage [19, 69].
Together, these data suggest that CASP6 released from axonal terminals regulates microglial TNF-[alpha] secretion, synaptic plasticity, and chronic pain (Figure 2(b)).
There is increasing evidence that CASP1, CASP6, and CASP11 activation is involved in microglia activation and the maturation of proinflammatory cytokines in inflammatory and neuropathic pain conditions [19, 38, 53, 63].
It is worth noting that CASP6 inhibition attenuates mechanical allodynia in male, but not in female, mice .
Skolnick, "TASSER: an automated method for the prediction of protein tertiary structures in CASP6
," Proteins, vol.
Findings from a study on apoptotic events in satellite cells derived from aged adults showed that, compared to young satellite cells, aged satellite cells are more vulnerable to apoptosis at all time points of the experiment (4 to 72 hours) with upregulation of CASP6
and CASP9 genes, while FADD gene is downregulated leading to decreased survival rate of satellite cells which results in decreased muscle regenerative capability  and finally muscle wasting.
TABLA III PATRON DE LATENCIA DEL VIRUS EPSTEIN BARR Y NEOPLASIAS ASOCIADAS Latencia Genes virales Neoplasias asociadas expresados I EBNA-1 Linfoma de Burkit EBERs BARF II EBNA-1 Linfoma de Hodgkin EBERs Cancer nasofaringeo LMP-1 Linfoma periferico LMP-2 T/NK BARF III Todos EBNAs Linfomas asociados a EBERs SIDA LMP-1 Desordenes LMP-2 linfoproliferativos BARF Postransplantes TABLA IV GENES CANDIDATOS Y LINFOMAS FAMILIARES Via Genes Ciclo celular/ AICDA, BAX, BCL2,BCL2A1,BCL2L1,BCL2L2, BCL2L10, Apoptosis BCL2L11(BIM), BCL6, BCL7A, BCL7C, BCL10, CASP1, CASP14, CASP4, CASP5, CASP6
, CASP7, CASP8AP2, CASP9, CCND1, LMO2, MYC, PIM1, RIPK1, RIPK2, TP53, TP53I.
Effector caspases (CASP3, CASP6
, CASP7) in turn cleave other protein substrates within the cell, to trigger the apoptotic process.
Consistent with 15 nM LBH589 being a sublethal concentration based on the absence of morphological cell apoptotic features, no detectable loss of cell number, and similar proportion of early apoptotic cells to DMSO control following 48 hours culture, our gene expression data demonstrated increased expression of antiapoptotic genes (BIRC3, BCL2L2, and CFLAR) and decreased expression of proapoptotic genes (CASP3, BCL2L11, CARD8, CASP6
, BNIP1, BCLAF1, CASP2, and APAF1) following LBH589 treatment (Figure 3).
Ahmed, "Combined suppression of CASP2 and CASP6
protects retinal ganglion cells from apoptosis and promotes axon regeneration through CNTF-mediated JAK/STAT signalling," Brain, vol.
MacCallum et al., "CASP6
assessment of contact prediction" Proteins, vol.