Fig. 6: The interaction network between CHI3L1 and its target proteins and the roles of CHI3L1 in signaling pathways for the development of neurological diseases.

a Alzheimer’s disease. Upper panel: The circle sizes are determined based on the score. The values in the circle symbols are the scores determined by STRING analysis. Lower panel: CHI3L1 regulates IL-6, inducing an increase in IL-1β and TNF-α. This pathway leads to the disruption of the blood‒brain barrier (BBB) and triggers neuroinflammation, ultimately resulting in neuronal death. IL-6 activates astrocytes, and reactive astrocytes (with increased GFAP) induce Aβ aggregation and Tau phosphorylation. They can also induce Aβ aggregation through the ApoE4 pathway, ultimately leading to neuronal death and cognitive impairment. CHI3L1 downregulates VSNL1 and increases Tau phosphorylation. CHI3L1 activates STAT3 and increases APP expression in neuronal cells, resulting in Aβ aggregation and cognitive impairment. b Schizophrenia. Upper panel: The circle sizes are determined based on the score. The values in the circle symbols are the scores determined by STRING analysis. Lower panel: CHI3L1 regulates IL-6, inducing microglial activation. Activated microglia express IL-6, IL-1β, and TNF-α, which leads to neuroinflammation and triggers abnormal neurotransmitter signaling. Ultimately, this process results in schizophrenia and related behavioral and immune dysfunction. The association score between CHI3L1 and CRP is high, indicating a strong correlation. However, the specific interaction between these two factors has not yet been identified. CRP is increased by inflammatory cytokines (IL-6, IL-1β, and TNF-α) and induces systemic inflammation, leading to immune dysfunction via the AKT1 pathway. CHI3L1 regulates TNF-α and induces immune dysfunction through the CD14-TLR4 pathway.