Disease relevance of Bace1

• Moreover, the levels of mature BACE1 were increased in human neuroblastoma cell line, SH-SY5Y, stably expressing wild-type PS1, compared to native cells [1].
• Taking together, these results show that recombinant adenoviruses expressing TS and ASP-2 antigens of T. cruzi are interesting candidates for the development of a vaccine against Chagas' disease [2].

Psychiatry related information on Bace1

• BACE knockout mice are healthy despite lacking the primary beta-secretase activity in brain: implications for Alzheimer's disease therapeutics [3].
• Importantly, Tg6799 mice engineered to lack the major Alzheimer's beta-secretase (beta-site APP-cleaving enzyme 1: BACE1) showed behavioral rescue from temporal memory deficits [4].

High impact information on Bace1

• Further mechanistic studies showed an altered neuregulin-Akt signaling pathway in Bace1-null mice [5].
• We show here that Bace1 regulates the process of myelination and myelin sheath thickness in the central and peripheral nerves [5].
• Bace1 modulates myelination in the central and peripheral nervous system [5].
• One locus, Asp-1, is located on chromosome 12 between Ah and D12Nyu1; another locus, Asp-2, is on chromosome 4, tightly linked to b [6].
• Here we report evidence that Asp-2 is located within an 8-centimorgan segment distal to b and that Asp-3 is linked to Mtv-1 on chromosome 7 [6].

Biological context of Bace1

• The predicted amino acid sequences of ASP-1 and ASP-2 were screened for H-2b allele-specific class I peptide motifs, and four peptides (PA11, PA12, PA13, and PA14) and six peptides (PA5, PA6, PA7, PA8, PA9, and PA10) were synthesized from ASP-1 and ASP-2, respectively [7].
• However, the pool of three ts genes provided no greater protection than the most effective single gene (ASP-2) either with or without coadministration of cytokine plasmids [8].
• In the backcross to the EP parent, no significant associations were found between AGS susceptibility and microsatellite markers linked to Asp1 or Asp2, AGS genes located on Chromosomes 12 and 4, respectively [9].
• The negative correlation of brain stem Ca2(+)-ATPase activity and AGS susceptibility in the BXD RI strains suggests that the strain difference in Ca2(+)-ATPase activity is inherited as a polygenic trait and that Asp-1 and Asp-2 are linked to, or identical to, factors that influence Ca2(+)-ATPase activity [10].

Anatomical context of Bace1

• The numbers of reactive astrocytes expressing BACE1 were increased in APP compared with APP/GRKO mice in both cortex and hippocampus [11].
• We show that the levels of exogenous and endogenous mature BACE1 expressed in presenilin-deficient mouse embryonic fibroblasts (PS-/-MEFs) were reduced significantly compared to those in wild-type MEFs [1].
• Immunity was completely reversed by the in vivo depletion of CD8(+) T cells, but not CD4(+) T cells, and was associated with the presence of CD8(+) T cells specific for an epitope located between amino acids 320 and 327 of ASP-2 [12].
• Immunization of mice with plasmids encoding ASP-1, ASP-2, or TSA-1 elicited poor antigen-specific cytotoxic-T-lymphocyte (CTL) activity and T. cruzi-specific antibody responses [8].

Associations of Bace1 with chemical compounds

• Staining by Asp1 and Asp2 was also inhibited by free small molecules containing aspartate [13].
• In all 3 types of assays, Asp1 and Asp2 displayed strong reactivity for small molecules and conjugates containing aspartate and little reactivity for small molecules and conjugates containing glutamate or GABA [13].
• The vaccination of mice with glutathione S-transferase fusion proteins representing amino acids 261 to 500 or 261 to 380 of ASP-2 in the presence of the adjuvants alum and CpG oligodeoxynucleotide 1826 provided remarkable immunity, consistently protecting 100% of the A/Sn mice [12].
• The acidic polysaccharide (ASP2, ASP3) consisted mainly of galacturonic acid along with rhamnose, arabinose, and galactose indicating a pectic polysaccharide [14].

Other interactions of Bace1

• Full-length neuregulin-1 was increased and its cleavage product was decreased in the CNS of Bace1-null mice [5].

Analytical, diagnostic and therapeutic context of Bace1

• A dominant negative mutant of signal transducer and activator of transcription 1 (STAT1) expression suppressed BACE1 promoter activity, and this was rescued by transfecting wild type STAT1 [15].
• Electrophoretic mobility shift assay and promoter activity assays indicated that STAT1 binds directly to the putative STAT1 binding sequence of BACE1 promoter [15].
• Here, we compared the protective efficacy and the immune response after individual or combined genetic vaccination of A/Sn mice with genes encoding trans-sialidase (TS) or the amastigote surface protein-2 (ASP-2) [16].

References