ChK1 activation induces reactive astrogliosis through CIP2A/PP2A/STAT3 pathway in Alzheimer's disease.

Cancerous Inhibitor of PP2A (CIP2A), an endogenous PP2A inhibitor, is upregulated and causes reactive astrogliosis, synaptic degeneration, and cognitive deficits in Alzheimer's disease (AD). However, the mechanism underlying the increased CIP2A expression in AD brains remains unclear. We here demonstrated that the DNA damage-related Checkpoint kinase 1 (ChK1) is activated in AD human brains and 3xTg-AD mice.

Upregulation of KDM6B contributes to lipopolysaccharide-induced anxiety-like behavior via modulation of VGLL4 in mice.

Histone H3K27me3 demethylase KDM6B (also known as Jumonji domain-containing protein D3, JMJD3) plays vital roles in the etiology of inflammatory responses; however, little is known about the role of KDM6B in neuroinflammation-induced anxiety-like behavior. The present study aimed to investigate the potential role of KDM6B in lipopolysaccharide (LPS)-induced anxiety-like behavior and to evaluate whether it is associated with the modulation of vestigial-like family member 4 (VGLL4). The elevated plus maze, light-dark box, and open-field test were performed to test the anxiety-like behavior induced by LPS in C57BL/6 J male mice.

Polyphyllin I attenuates cognitive impairments and reduces AD-like pathology through CIP2A-PP2A signaling pathway in 3XTg-AD mice.

Polyphyllin I (PPI) is a natural phytochemical drug isolated from plants which can inhibit the proliferation of cancer cells. One of the PPI tumor-inhibitory effects is through downregulating the expression of Cancerous Inhibitor of PP2A (CIP2A), the latter, is found upregulated in Alzheimer's disease (AD) brains and participates in the development of AD. In this study, we explored the application of PPI in experimental AD treatment in CIP2A-overexpressed cells and 3XTg-AD mice.