mRNA Levels of BACE1 and its interacting proteins, RTN3 and PPIL2, correlate in human post mortem brain tissue

N. Beyer, D. T. R. Coulson, J. G. Quinn, S. Brockbank, J. Hellemans, G. B. Irvine, R. Ravid, J. A. Johnston

Research output: Contribution to journalArticle

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Abstract

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 qbasePLUS, 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.
Original languageEnglish
Pages (from-to)44-42
Number of pages9
JournalNeuroscience
Volume274
Early online date20 May 2014
DOIs
Publication statusPublished - 22 Aug 2014

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Peptidylprolyl Isomerase
Cyclophilins
Amyloid Precursor Protein Secretases
Messenger RNA
Brain
Alzheimer Disease
Proteins
Phosphopyruvate Hydratase
Glial Fibrillary Acidic Protein
Amyloid beta-Protein Precursor
Enzymes
Real-Time Polymerase Chain Reaction
Peptide Hydrolases
Gene Expression
Peptides
Research
Population
Genes

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Beyer, N. ; Coulson, D. T. R. ; Quinn, J. G. ; Brockbank, S. ; Hellemans, J. ; Irvine, G. B. ; Ravid, R. ; Johnston, J. A. / mRNA Levels of BACE1 and its interacting proteins, RTN3 and PPIL2, correlate in human post mortem brain tissue. In: Neuroscience. 2014 ; Vol. 274. pp. 44-42.
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mRNA Levels of BACE1 and its interacting proteins, RTN3 and PPIL2, correlate in human post mortem brain tissue. / Beyer, N.; Coulson, D. T. R.; Quinn, J. G.; Brockbank, S.; Hellemans, J.; Irvine, G. B.; Ravid, R.; Johnston, J. A.

In: Neuroscience, Vol. 274, 22.08.2014, p. 44-42.

Research output: Contribution to journalArticle

TY - JOUR

T1 - mRNA Levels of BACE1 and its interacting proteins, RTN3 and PPIL2, correlate in human post mortem brain tissue

AU - Beyer, N.

AU - Coulson, D. T. R.

AU - Quinn, J. G.

AU - Brockbank, S.

AU - Hellemans, J.

AU - Irvine, G. B.

AU - Ravid, R.

AU - Johnston, J. A.

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AB - 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 qbasePLUS, 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.

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