Interaction between TRPML1 and p62 in Regulating Autophagosome-Lysosome Fusion and Impeding Neuroaxonal Dystrophy in Alzheimer’s Disease

Figure 1

Overexpression of TRPML1 alleviates NAD and cognitive impairment in mice with Alzheimer-like phenotypes. (a) A volcano plot of differential gene expression analysis of the AD-related GSE5281 dataset. The abscissa represents -log10 ( value), the ordinate represents the logFC value, the red dots represent highly expressed genes, and the green dots represent poorly expressed genes. (b) Venn diagram of AD-related genes from the GeneCards and DisGeNet databases as well as differentially underexpressed genes. (c) A heat map of candidate gene expression in the AD-related GSE5281 dataset. The color scale from green to red indicates that the gene expression value is from low to high. (d) Expression of TRPML1 in AD samples () and control samples () in the AD-related GSE5281 dataset. (e) The protein expression of TRPML1 in the hippocampal tissues of APP/PS1 mice, determined by Western blot analysis. (f) The protein expression of TRPML1 in the hippocampal tissues of APP/PS1 mice in the absence or presence of TRPML1^+/+, determined by Western blot analysis. (g) Escape latency of APP/PS1 mice in the absence or presence of TRPML1^+/+. (h) The travel length of APP/PS1 mice in the absence or presence of TRPML1^+/+. (i) Time crossing the platform of APP/PS1 mice in the absence or presence of TRPML1^+/+. (j) Recognition indexes of APP/PS1 mice in the absence or presence of TRPML1^+/+. (k) Expression of TRPML1 in primary neurons in response to Aβ1-42 alone or combined with oe-TRPML1/sh-TRPML1, determined by Western blot analysis. (l) Axonal length of neurons observed under an inverted microscope. Measurement data were described as the . An unpaired -test was used for comparison between the two groups. One-way ANOVA was used for comparisons among multiple groups, followed by Tukey’s post hoc test. ANOVA of repeated measurements with Bonferroni’s post hoc test was applied for multigroup comparisons at different time points. for mice in each group. vs. C57BL/6J WT mice or untreated primary hippocampal neurons; ^# vs. APP/PS1 mice; ^{^} vs. primary hippocampal neurons treated with sh-NC+Aβ1-42; ^& vs. primary hippocampal neurons treated with oe-NC+Aβ1-42. The cell experiment was repeated 3 times independently.

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