Transcriptome analyses of 7-day-old zebrafish larvae possessing a familial Alzheimer's disease-like mutation in psen1 indicate effects on oxidative phosphorylation, ECM and MCM functions, and iron homeostasis.
Yang DongMorgan NewmanStephen M PedersonKarissa BarthelsonNhi HinMichael LardelliPublished in: BMC genomics (2021)
Our analyses predicted a significant effect on oxidative phosphorylation, consistent with our earlier observations of predicted effects on ATP synthesis in adult heterozygous psen1Q96_K97del brains. The dysregulation of minichromosome maintenance protein complex (MCM) genes strongly contributed to predicted effects on DNA replication and the cell cycle and may explain earlier observations of genome instability due to PSEN1 mutation. The upregulation of crystallin gene expression may be a response to defective activity of mutant Psen1 protein in endolysosomal acidification. Genes related to extracellular matrix (ECM) were downregulated, consistent with previous studies of EOfAD mutant iPSC neurons and postmortem late onset AD brains. Also, changes in expression of genes controlling iron ion transport were observed without identifiable changes in the prevalence of transcripts containing iron responsive elements (IREs) in their 3' untranslated regions (UTRs). These changes may, therefore, predispose to the apparent iron dyshomeostasis previously observed in 6-month-old heterozygous psen1Q96_K97del EOfAD-like mutant brains.
Keyphrases
- early onset
- late onset
- extracellular matrix
- cell cycle
- genome wide
- gene expression
- cell proliferation
- poor prognosis
- iron deficiency
- dna methylation
- wild type
- genome wide identification
- bioinformatics analysis
- binding protein
- spinal cord
- risk factors
- protein kinase
- protein protein
- genome wide analysis
- magnetic resonance imaging
- transcription factor
- small molecule
- rna seq
- diffusion weighted imaging
- zika virus
- drug delivery
- long non coding rna
- mild cognitive impairment
- aedes aegypti