ArticleMolecular & cellular proteomics : MCP2012
The amyloid precursor protein (APP) family members are key players in S-adenosylmethionine formation by MAT2A and modify BACE1 and PSEN1 gene expression-relevance for Alzheimer's disease.
Article in Molecular & cellular proteomics : MCP, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 33 citations in OpenAlex.
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- Integrative multi-omics landscape of fluoxetine action across 27 brain regions reveals global increase in energy metabolism and region-specific chromatin remodelling.Molecular psychiatry · 2022Article
- Essential Roles of Peroxiredoxin IV in Inflammation and Cancer.Molecules (Basel, Switzerland) · 2022Review
- Finding New Ways How to Control BACE1.The Journal of membrane biology · 2022Article
- Revelation of Pivotal Genes Pertinent to Alzheimer's Pathogenesis: A Methodical Evaluation of 32 GEO Datasets.Journal of molecular neuroscience : MN · 2022Article
- Peroxiredoxins in Neurodegenerative Diseases.Antioxidants (Basel, Switzerland) · 2020Review
- CpG and non-CpG Presenilin1 methylation pattern in course of neurodevelopment and neurodegeneration is associated with gene expression in human and murine brain.Epigenetics · 2020Article
- Genome-Wide Association Study Identifies Genomic Loci Affecting Filet Firmness and Protein Content in Rainbow Trout.Frontiers in genetics · 2019Article
- Precipitation with polyethylene glycol followed by washing and pelleting by ultracentrifugation enriches extracellular vesicles from tissue culture supernatants in small and large scales.Journal of extracellular vesicles · 2018Article
- Altered protein phosphorylation as a resource for potential AD biomarkers.Scientific reports · 2016Article
- Approaches to Investigating Complex Genetic Traits in a Large-Scale Inbred Mouse Aging Study.Veterinary pathology · 2016Article
- Role of Pex21p for Piggyback Import of Gpd1p and Pnc1p into Peroxisomes of Saccharomyces cerevisiae.The Journal of biological chemistry · 2015Article
- Amyloid beta a4 precursor protein-binding family B member 1 (FE65) interactomics revealed synaptic vesicle glycoprotein 2A (SV2A) and sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) as new binding proteins in the human brain.Molecular & cellular proteomics : MCP · 2014Article
- The cytosolic domain of Pex22p stimulates the Pex4p-dependent ubiquitination of the PTS1-receptor.PloS one · 2014Article
- Metabolic Dysfunction of Astrocyte: An Initiating Factor in Beta-amyloid Pathology?Aging and neurodegeneration · 2013Article
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9 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Central hallmark of Alzheimer's disease are senile plaques mainly composed of β-amyloid, which is a cleavage product of the amyloid precursor protein (APP). The physiological function of APP and its family members APLP1 and APLP2 is poorly understood. In order to fill this gap, we established a cell-culture based model with simultaneous knockdown of all members of the family. A comprehensive proteome study of the APP/APLP1/APLP2 knockdown cell lysates versus controls revealed significant protein abundance changes of more than 30 proteins. Targeted validation of selected candidates by immunoblotting supported the significant down-regulation of the methionine adenosyltransferase II, alpha (MAT2A) as well as of peroxiredoxin 4 in the knockdown cells. Moreover, MAT2A was significantly down-regulated at the mRNA level as well. MAT2A catalyzes the production of S-adenosylmethionine from methionine and ATP, which plays a pivotal role in the methylation of neurotransmitters, DNA, proteins, and lipids. MAT2A-dependent significant up-regulation of S-adenosylmethionine was also detectable in the knockdown cells compared with controls. Our results point to a role of the APP family proteins in cellular methylation mechanisms and fit to findings of disturbed S-adenosylmethionine levels in tissue and CSF of Alzheimer disease patients versus controls. Importantly, methylation plays a central role for neurotransmitter generation like acetylcholine pointing to a crucial relevance of our findings for Alzheimer's disease. In addition, we identified differential gene expression of BACE1 and PSEN1 in the knockdown cells, which is possibly a consequence of MAT2A deregulation and may indicate a self regulatory mechanism.
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