Leptin Regulates Tau Phosphorylation through Wnt Signaling Pathway in PC12 Cells

Abstract

Background/Aims: Leptin, an adipocytokine produced endogenously in the brain, is decreased in Alzheimer's disease(AD) and has also been shown to reduce Aβ levels in vitro and in vivo. Sets of evidence show that leptin reduces Aβ production and tau phosphorylation in neuronal cells and transgenic mice models of AD. Herein, we investigated the signaling pathway activated by leptin, to better understand its mechanism of action. Methods: Western blotting was performed to assess the levels of phosphor-tau and Bax, RT-PCR to check the mRNA level of Bax. Results: Leptin treatment significantly blunted Aβ-evoked tau phosphorylation and Bax levels, effects of which could be reversed by antagonist of Wnt signaling. Conclusion: The data indicate that Leptin may provide a novel therapeutic approach to AD treatment via wnt signaling.

Spatiotemporally deciphering the mysterious mechanism of persistent HPV‐induced malignant transition and immune remodelling from HPV‐infected normal cervix, precancer to cervical cancer: Integrating single‐cell RNA‐sequencing and spatial transcriptome

“…Notably, we observed that clusters 1 and 3 were mainly enriched in the normal group, cluster 2 was remarkably clustered in HSIL, and clusters 6, 7, 9 and 13 were prominent in CC (Figure 2C). Moreover, by analysing the marker gene expression and functional pathways of these ‘HPV‐related clusters,’ we discovered that clusters 1 and 3 enriched in the normal cervix featured antineoplastic effects and highly expressed multiple tumour suppressors (SLC5A8, DERL3) (Figure 2D), thereby suppressing cell proliferative, migratory and invasive capacities 9,10 . On the other hand, cluster 2, representing HSIL, manifested high cellular motor capacity, specifically expressing genes related to cell adhesion (CDH16, CDH17 and VSIG1) 11,12 and extracellular matrix degradation (CTSE) (Figure 2E), thus potentially promoting the expansion of atypical cells in intraepithelial neoplasia progression.…”

“…Moreover, by analysing the marker gene expression and functional pathways of these ‘HPV‐related clusters,’ we discovered that clusters 1 and 3 enriched in the normal cervix featured antineoplastic effects and highly expressed multiple tumour suppressors (SLC5A8, DERL3) (Figure 2D ), thereby suppressing cell proliferative, migratory and invasive capacities. 9 , 10 On the other hand, cluster 2, representing HSIL, manifested high cellular motor capacity, specifically expressing genes related to cell adhesion (CDH16, CDH17 and VSIG1) 11 , 12 and extracellular matrix degradation (CTSE) (Figure 2E ), thus potentially promoting the expansion of atypical cells in intraepithelial neoplasia progression. Additionally, we observed that clusters 6, 7, 9 and 13 (CASP14, PRSS27, CALML5) (Figure 2F ), which were enriched in CC, manifested high expression levels of genes related to carcinogenic pathways such as epithelial‐to‐mesenchymal transition, tumour cell proliferation, migration, invasion and angiogenesis.…”

“…For cervical epithelial cells, (1) we, for the first time, identified and creatively named three ‘HPV‐related clusters’ unique to distinct disease stages. Among them, the ‘HPV‐related normal cluster’ specifically expressed SLC5A8, a tumour suppressor gene, which has been reported to inhibit cell proliferation and regulate cell apoptosis 9,43 . This finding indicated that the protective mechanism would be activated accordingly after HPV infection.…”

Association of late-life body mass index with the risk of Alzheimer disease: a 10-year nationwide population-based cohort study

“…Leptin reduces the production of Aβ from amyloid precursor proteins by inhibiting the γ-secretase complex 10 and diminishes extracellular Aβ by driving Aβ uptake into cells 11 . Leptin inhibits the production of hyperphosphorylated tau that forms neurofibrillary tangles, which are the key pathological features of AD 11 , 12 . The correlation between plasma leptin levels and body fat is known to persist with age and appear in older adults 35 .…”

“…The exact underlying mechanisms are still unclear but one plausible explanation for this might be due to the fat-derived hormone leptin 6 . A previous study showed that higher plasma leptin levels were associated with a lower risk of AD 9 , suggesting leptin may play a role in reducing the production of amyloid beta (Aβ) 10 , diminishing extracellular Aβ 11 , and inhibiting the production of hyperphosphorylated tau which are the key pathological features of AD 11 , 12 .…”