Observations of the interactions between the inflammatory cytokine interleuldn-1 (IL-1) beta and the inflammatory/apoptotic caspase-1 and their involvement in age-related impairments in cognition. A comprehensive understanding of these mechanisms could potentially lead to the development of preventive or protective therapies that reduce or inhibit the cognitive decline associated with aging and age-related neurodegenerative disease 1).
Blockade of caspase-1 increases neurogenesis in the aged hippocampus 2).
The caspase 1 T activation complexes (inflammasomes) can facilitate caspase-1 and IL-1β processing, which amplifies the inflammatory response. In a study Li et al. examined whether caspase-1 activation contributes to irradiation-induced damage to neural stem and progenitor cells (NSPCs). They found that X-ray irradiation induced activation of caspase-1 in NSPCs in vitro and in vivo. Next, using a caspase-1 inhibitor (Ac-YVAD-CMK) to block caspase-1 activation in vitro and in vivo, we further demonstrated that X-ray irradiation may inhibit proliferation, induce senescence of NSPCs through caspase-1 activation. Together, these results suggest that caspase-1 activation is involved in irradiation-induced damage to NSPCs 3)
Rashad et al., from Sendai, Japan showed the intense activation of immune cells, particularly the microglia, along with the increase in macrophage activity and NLRP3 inflammasome activation that is indicated by NLRP3, Interleukin 1 beta (IL-1β), and Interleukin 18 gene and caspase 1 upregulation and cleavage as well as pyroptosis.
Leukocytes were observed in the brain parenchyma, indicating a role in cerebral venous thrombosis (CVT)-induced inflammation. In addition, astrocytes were activated, and they induced glial scar leading to parenchymal contraction during the subacute stage and tissue loss. MMP9 was responsible primarily for the BBB breakdown after CVT and it is mainly produced by pericytes. MMP9 activation was observed before inflammatory changes, indicating that BBB breakdown is the initial driver of the pathology of CVT. These results show an inflammation driven pathophysiology of CVT that follows MMP9-mediated BBB breakdown, and identified several targets that can be targeted by pharmaceutical agents to improve the neuroinflammation that follows CVT, such as MMP9, NLRP3, and IL-1β. Some of these pharmaceutical agents are already in clinical practice or under clinical trials indicating a good potential for translating this work into patient care 4).