Q-VD-OPH

The Zika virus (ZIKV) has gained attention due to its link with causing congenital syndrome, which is characterized by microcephaly as a significant symptom. The neurotropism of the virus is not limited to neural progenitor cells; ZIKV has also been tested as an oncolytic virus, given its affinity for tumor cells in the central nervous system. Understanding the cell death pathway involved in eliminating tumor cells is crucial to determining whether ZIKV triggers a silent or immunogenic response in the nervous tissue, which could potentially harm the surrounding healthy tissue. Hence, this study investigated the cell death pathways in human embryonal central nervous tumor cells that were either infected or not infected with ZIKV using in vitro assays. The cells were treated with specific inhibitors of proteins associated with apoptosis, necroptosis, and pyroptosis and then analyzed using flow cytometry and Western blotting. The results demonstrated that these cells could activate apoptosis, necroptosis and pyroptosis as cell death pathways. However, unlike the blockers for necroptosis and pyroptosis proteins, only caspase inhibition with Q-VD-OPh successfully protects all cells from dying after ZIKV infection. ZIKV predominantly induces apoptosis to eradicate central nervous tumor cells promoting low immunogenic profile, which suggests that ZIKV can effectively infect and eliminate tumor cells while sparing surrounding healthy tissue.

Alzheimer's disease (AD) is a neurodegenerative disease with a significant impact on global public health. The primary hallmarks of the disease included amyloid-beta peptide (Aβ) deposition, neurofibrillary tangles (NFT), and synaptic loss. Sirtuins, a group of NAD⁺-dependent deacetylase enzymes, are key regulators of AD pathogenesis. SIRT1, a member of sirtuins, has been identified to possess neuroprotective properties. Thus, its promising enhancers are included. Further, SIRT2 promising inhibitors are reviewed for therapeutic efficacy. The extrinsic and intrinsic apoptotic pathways of caspases are mediated by CD95 and DNA damage. The promising inhibitors Q-VD-OPh and minocycline are found to be specific for caspase-7 and caspase-3, respectively. Primarily, glycogen synthase kinase-3β (GSK-3β) is found to be involved in the generation of phosphorylated tau. The promising GSK-3 inhibitor included the COB-187 (IC₅₀ = 370 nM) and maleimide-derivative (compound 33, IC₅₀ = 0.09 μM). This review highlights the molecular mechanisms of sirtuin, caspase, and GSK-3 in the pathophysiology of AD. Further, promising modulators specific to these targets are described.