Research Paper Volume 16, Issue 3 pp 1983—2004

Figure 6. Effect of GV1001 on aging, telomere maintenance, and long-term memory confirmed via bioinformatics analysis. (A) ClueGO analysis visualised the significant functional enrichment results of upregulated and downregulated mRNAs associated with inflammation in old-aged 3xTg-AD mice treated with GV1001 compared to those treated with saline, using the Gene Ontology (GO) functional network. mRNAs that show significant differential expression are selected for analyses based on the following criteria: more than three-fold change, normalised data (log2) >4, and p < 0.05. The functionally grouped networks of the gene regulatory network and the target genes of these hub nodes were transferred to ClueGO and grouped as functional clusters. All nodes have been linked based on their kappa scores (≥0.3). Only the most significant term per group is labelled in bold, and their colours represent the functional groups to which they belong. Node size represents enrichment significance. (B) Proteomics show that GV1001 affected the levels of various intracellular proteins in the brains of 3xTg AD mice. Two-dimensional (2D) gel electrophoresis images. The first dimension is run using a 13-cm IPG strip with a pH gradient from 4 to 10. Coomassie blue staining is used to identify 24 proteins that increased or decreased more than two-fold. (C) Heat map shows protein levels. Protein expression values are log2-transformed. Red indicates a high expression level; green indicates a low expression level. (D) STRING analysis (functional protein association networks database, http://string-db.org/) of upregulated and downregulated proteins. Proteins are clustered based on the STRING evidence score. PPA2, inorganic pyrophosphatase 1; GSTM1, glutathione S-transferase Mu 1 isoform 2; MICOS, mitochondrial contact site and cristae organising system; CHCHD3, complex subunit Mic19; PRDX1, peroxiredoxin-1; DPYSL2, dihydropyrimidinase-related protein 2; OXCT1, succinyl-CoA:3-ketoacid coenzyme A transferase 1; TYBB2A, tubulin beta-2A chain isoform 1; SPTAN1, spectrin alpha 2; PHB, prohibitin; TKT, transketolaseHSP90AA1, HSP90AA1, heat shock protein 90 alpha class A member 1; HSP90AB1, heat shock protein 90 alpha class B member 1.