mRNA levels of BACE1 and its interacting proteins, RTN3 and PPIL2, correlate in human post mortem brain tissue.
β-Site amyloid precursor protein cleaving enzyme (BACE1) is the rate-limiting enzyme for production of Aβ peptides, proposed to drive the pathological changes found in Alzheimer's disease (AD). Reticulon 3 (RTN3) is a negative modulator of BACE1 (β-secretase) proteolytic activity, while peptidylprolyl isomerase (cyclophilin)-like 2 (PPIL2) positively regulated BACE1 gene expression in a cell-based assay. This study aimed to analyze RTN3 and PPIL2 mRNA levels in four brain regions from individuals with AD and controls. BACE1 mRNA had been previously quantified in the samples, as had glial fibrillary acidic protein (GFAP) and neuron-specific enolase (NSE), to track changing cell populations in the tissue. mRNA levels in the human post mortem brain tissue were assayed using quantitative real-time polymerase chain reaction (qPCR) and qbase(PLUS), employing validated stably expressed reference genes. No differences in RTN3 or PPIL2 mRNA levels were found in individuals with AD, compared to controls. Both RTN3 and PPIL2 mRNA levels correlated significantly with BACE1 mRNA and all three showed similar disease stage-dependent changes with respect to NSE and GFAP. These findings indicated that the in vitro data demonstrating an effect of PPIL2 on BACE1 expression have functional relevance in vivo. Further research into BACE1-interacting proteins could provide a fruitful approach to the modulation of this protease and consequently Aβ production.
Queen's University Belfast, School of Medicine, Dentistry and Biomedical Sciences, Northern Ireland, United Kingdom.
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N
Beyer
Queen's University Belfast, School of Medicine, Dentistry and Biomedical Sciences, Northern Ireland, United Kingdom.
D T R
DT
Coulson
Queen's University Belfast, School of Medicine, Dentistry and Biomedical Sciences, Northern Ireland, United Kingdom.
J G
JG
Quinn
Queen's University Belfast, School of Medicine, Dentistry and Biomedical Sciences, Northern Ireland, United Kingdom.
S
S
Brockbank
Center for Medical Genetics Ghent, Ghent University, B-9000 Ghent, Belgium.
J
J
Hellemans
Queen's University Belfast, School of Medicine, Dentistry and Biomedical Sciences, Northern Ireland, United Kingdom.
G B
GB
Irvine
Brain Bank Consultants, PO Box 882, 1180 AW Amstelveen, The Netherlands; Netherlands Institute for Neurosciences, Meibergdreef 47, 1105 BA Amsterdam, The Netherlands.
R
R
Ravid
Queen's University Belfast, School of Medicine, Dentistry and Biomedical Sciences, Northern Ireland, United Kingdom. Electronic address: janetjo65@gmail.com.
J A
JA
Johnston
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D053829:Amyloid Precursor Protein Secretases / Q000032:analysis*; D016282:Aspartic Acid Endopeptidases / Q000032:analysis*; D001921:Brain / Q000378:metabolism*; D002352:Carrier Proteins / Q000032:analysis*; D021983:Cyclophilins / Q000032:analysis*; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000032:analysis*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000032:analysis*; D012333:RNA, Messenger / Q000032:analysis
D002352:Carrier Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C476198:RTN3 protein, human; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; D021983:Cyclophilins; C099773:PPIL2 protein, human
Braak staging; amyloid precursor protein secretase; gene expression; protease; qPCR; reference gene