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a Boxplot of human parahippocampal transcriptome data from MSBB showing activated PKN1-5a1 cryptic splicing in AD samples across Braak stages. Box plots show median (center line), the upper and lower quantiles (box), and the range of the data (whiskers). b Schematic of bilateral hippocampal AAV injection in C57BL/6J mice and subsequent behavioral testing. c Morris water maze showing prolonged escape latency in AAV-PKFL and AAV-PKN207 mice <t>(AAV-CTR</t> n = 9, AAV-PKFL n = 10, AAV-PKN207 n = 10, repeated-measures two-way ANOVA). d CSF NEFL levels are elevated in AAV-PKN207 mice (AAV-CTR n = 10, AAV-PKFL n = 20, AAV-PKN207 n = 20; one-way ANOVA). e Primary hippocampal neurons expressing PKFL or PKN207 showing increased LDH release ( n = 4, one-way ANOVA). f KEGG enrichment of DEPs highlights pathways linked to synaptic function and neurodegeneration. g Heatmap showing downregulation of LTP-related genes in PKN207-expressing mice. h STRING network of NEFL-interacting proteins (red: upregulated; blue: downregulated). i Western blots of neurofilament proteins in N2a cells overexpressing PKFL or PKN207. j Hippocampal LTP is impaired in AAV-PKN207 mice; fEPSP slopes are shown (5 mice, 10 slices; one-way ANOVA). Source data are provided as a Source Data file.
Aav Ctr, supplied by Bioprofile Testing, used in various techniques. Bioz Stars score: 86/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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a Boxplot of human parahippocampal transcriptome data from MSBB showing activated PKN1-5a1 cryptic splicing in AD samples across Braak stages. Box plots show median (center line), the upper and lower quantiles (box), and the range of the data (whiskers). b Schematic of bilateral hippocampal AAV injection in C57BL/6J mice and subsequent behavioral testing. c Morris water maze showing prolonged escape latency in AAV-PKFL and AAV-PKN207 mice (AAV-CTR n = 9, AAV-PKFL n = 10, AAV-PKN207 n = 10, repeated-measures two-way ANOVA). d CSF NEFL levels are elevated in AAV-PKN207 mice (AAV-CTR n = 10, AAV-PKFL n = 20, AAV-PKN207 n = 20; one-way ANOVA). e Primary hippocampal neurons expressing PKFL or PKN207 showing increased LDH release ( n = 4, one-way ANOVA). f KEGG enrichment of DEPs highlights pathways linked to synaptic function and neurodegeneration. g Heatmap showing downregulation of LTP-related genes in PKN207-expressing mice. h STRING network of NEFL-interacting proteins (red: upregulated; blue: downregulated). i Western blots of neurofilament proteins in N2a cells overexpressing PKFL or PKN207. j Hippocampal LTP is impaired in AAV-PKN207 mice; fEPSP slopes are shown (5 mice, 10 slices; one-way ANOVA). Source data are provided as a Source Data file.

Journal: Nature Communications

Article Title: A neurotoxic cryptic peptide arising from TDP-43-dependent cryptic splicing of PKN1

doi: 10.1038/s41467-026-68916-0

Figure Lengend Snippet: a Boxplot of human parahippocampal transcriptome data from MSBB showing activated PKN1-5a1 cryptic splicing in AD samples across Braak stages. Box plots show median (center line), the upper and lower quantiles (box), and the range of the data (whiskers). b Schematic of bilateral hippocampal AAV injection in C57BL/6J mice and subsequent behavioral testing. c Morris water maze showing prolonged escape latency in AAV-PKFL and AAV-PKN207 mice (AAV-CTR n = 9, AAV-PKFL n = 10, AAV-PKN207 n = 10, repeated-measures two-way ANOVA). d CSF NEFL levels are elevated in AAV-PKN207 mice (AAV-CTR n = 10, AAV-PKFL n = 20, AAV-PKN207 n = 20; one-way ANOVA). e Primary hippocampal neurons expressing PKFL or PKN207 showing increased LDH release ( n = 4, one-way ANOVA). f KEGG enrichment of DEPs highlights pathways linked to synaptic function and neurodegeneration. g Heatmap showing downregulation of LTP-related genes in PKN207-expressing mice. h STRING network of NEFL-interacting proteins (red: upregulated; blue: downregulated). i Western blots of neurofilament proteins in N2a cells overexpressing PKFL or PKN207. j Hippocampal LTP is impaired in AAV-PKN207 mice; fEPSP slopes are shown (5 mice, 10 slices; one-way ANOVA). Source data are provided as a Source Data file.

Article Snippet: Hippocampus stored at −80 °C from AAV-CTR, AAV-PKN207, and AAV-PKFL mice, with three biological replicates per group, following protein extraction and trypsin digestion, peptides were combined in equal amounts and submitted to Shanghai Bioprofile Biotechnology Co., Ltd. for data-independent acquisition (DIA) using the Orbitrap Astral platform.

Techniques: Injection, Expressing, Western Blot