Amyloidosis causes downregulation of SorLA, SorCS1 and SorCS3 expression in mice
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Amyloidosis causes downregulation of SorLA, SorCS1 and SorCS3 expression in mice. / Hermey, Guido; Hoffmeister-Ullerich, Sabine A; Merz, Barbara; Groß, Dagmar; Kuhl, Dietmar; Kins, Stefan.
In: BIOL CHEM, Vol. 400, No. 9, 27.08.2019, p. 1181-1189.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Amyloidosis causes downregulation of SorLA, SorCS1 and SorCS3 expression in mice
AU - Hermey, Guido
AU - Hoffmeister-Ullerich, Sabine A
AU - Merz, Barbara
AU - Groß, Dagmar
AU - Kuhl, Dietmar
AU - Kins, Stefan
PY - 2019/8/27
Y1 - 2019/8/27
N2 - Accumulation of β-amyloid peptide (Aβ) is regarded as a primary cause of Alzheimer's disease (AD). Aβ is derived by sequential cleavage of the amyloid precursor protein (APP). Alterations in the subcellular targeting of APP are thought to affect the degree of Aβ production. Sorting receptors, such as SorLA, convey subcellular targeting of APP. Dysfunction of SorLA, and likely of the related receptors SorCS1 and SorCS3, cause AD. Nevertheless, disease progression could also provoke altered expression of the receptors. Here, we assessed if Aβ plaque formation promotes altered expression of SorLA, SorCS1 and SorCS3. We analyzed transcript levels during aging and after amyloidosis in brain areas characterized by early amyloid plaque formation in an AD mouse model (APPPS1) and wild types. We observed stable expression levels during aging (1-12 months). After plaque formation, SorCS1 and SorLA expression were markedly reduced in the frontal cerebral cortex and to a minor extent in the hippocampus, whereas SorCS3 expression was solely reduced in the frontal cerebral cortex. Our results indicate that disease progression, associated with Aβ accumulation, can negatively regulate expression of the receptors.
AB - Accumulation of β-amyloid peptide (Aβ) is regarded as a primary cause of Alzheimer's disease (AD). Aβ is derived by sequential cleavage of the amyloid precursor protein (APP). Alterations in the subcellular targeting of APP are thought to affect the degree of Aβ production. Sorting receptors, such as SorLA, convey subcellular targeting of APP. Dysfunction of SorLA, and likely of the related receptors SorCS1 and SorCS3, cause AD. Nevertheless, disease progression could also provoke altered expression of the receptors. Here, we assessed if Aβ plaque formation promotes altered expression of SorLA, SorCS1 and SorCS3. We analyzed transcript levels during aging and after amyloidosis in brain areas characterized by early amyloid plaque formation in an AD mouse model (APPPS1) and wild types. We observed stable expression levels during aging (1-12 months). After plaque formation, SorCS1 and SorLA expression were markedly reduced in the frontal cerebral cortex and to a minor extent in the hippocampus, whereas SorCS3 expression was solely reduced in the frontal cerebral cortex. Our results indicate that disease progression, associated with Aβ accumulation, can negatively regulate expression of the receptors.
U2 - 10.1515/hsz-2019-0146
DO - 10.1515/hsz-2019-0146
M3 - SCORING: Journal article
C2 - 31095505
VL - 400
SP - 1181
EP - 1189
JO - BIOL CHEM
JF - BIOL CHEM
SN - 1431-6730
IS - 9
ER -