Inhibition of energy metabolism down-regulates the Alzheimer related presenilin 2 gene

R. Ghidoni; L. Gasparini; A. Alberici; L. Benussi; L. Barbiero; F. Mazzoli; F. Nicosia; D. Finazzi; L. Benerini Gatta; A. Albertini; O. Zanetti; G. Binetti

doi:10.1007/s00702-003-0015-9

Inhibition of energy metabolism down-regulates the Alzheimer related presenilin 2 gene

R. Ghidoni, L. Gasparini, A. Alberici, L. Benussi, L. Barbiero, F. Mazzoli, F. Nicosia, D. Finazzi, L. Benerini Gatta, A. Albertini, O. Zanetti, G. Binetti

Centro San Giovanni di Dio - Fatebenefratelli

Research output: Contribution to journal › Article › peer-review

Abstract

Defects in energy metabolism and oxidative stress play an important role in the pathogenesis of Alzheimer's Disease (AD). In sporadic AD cases, presenilin 2 (PS2) mRNA levels are decreased in brain areas affected by the disease. The aim of the present study was to investigate whether mitochondrial dysfunction might influence PS2 gene expression. We demonstrated that the inhibition of energy metabolism by sodium azide down-regulates PS2 gene expression through modification of promoter activity. No one of the analyzed transcription factors, sensitive to redox status of the cell, could explain this effect. Azide effect on PS2 expression was completely inhibited by the addition of an antioxidant suggesting that the imbalance of the cellular redox homeostasis modulates the expression of this gene.

Original language	English
Pages (from-to)	1029-1039
Number of pages	11
Journal	Journal of Neural Transmission
Volume	110
Issue number	9
DOIs	https://doi.org/10.1007/s00702-003-0015-9
Publication status	Published - Sep 1 2003

Keywords

Nonradioactive RPA
Oxidative stress
PS2 expression

ASJC Scopus subject areas

Neuroscience(all)

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10.1007/s00702-003-0015-9

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Inhibition of energy metabolism down-regulates the Alzheimer related presenilin 2 gene. / Ghidoni, R.; Gasparini, L.; Alberici, A.; Benussi, L.; Barbiero, L.; Mazzoli, F.; Nicosia, F.; Finazzi, D.; Gatta, L. Benerini; Albertini, A.; Zanetti, O.; Binetti, G.

In: Journal of Neural Transmission, Vol. 110, No. 9, 01.09.2003, p. 1029-1039.

Research output: Contribution to journal › Article › peer-review

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abstract = "Defects in energy metabolism and oxidative stress play an important role in the pathogenesis of Alzheimer's Disease (AD). In sporadic AD cases, presenilin 2 (PS2) mRNA levels are decreased in brain areas affected by the disease. The aim of the present study was to investigate whether mitochondrial dysfunction might influence PS2 gene expression. We demonstrated that the inhibition of energy metabolism by sodium azide down-regulates PS2 gene expression through modification of promoter activity. No one of the analyzed transcription factors, sensitive to redox status of the cell, could explain this effect. Azide effect on PS2 expression was completely inhibited by the addition of an antioxidant suggesting that the imbalance of the cellular redox homeostasis modulates the expression of this gene.",

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AU - Ghidoni, R.

AU - Gasparini, L.

AU - Alberici, A.

AU - Benussi, L.

AU - Barbiero, L.

AU - Mazzoli, F.

AU - Nicosia, F.

AU - Finazzi, D.

AU - Gatta, L. Benerini

AU - Albertini, A.

AU - Zanetti, O.

AU - Binetti, G.

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AB - Defects in energy metabolism and oxidative stress play an important role in the pathogenesis of Alzheimer's Disease (AD). In sporadic AD cases, presenilin 2 (PS2) mRNA levels are decreased in brain areas affected by the disease. The aim of the present study was to investigate whether mitochondrial dysfunction might influence PS2 gene expression. We demonstrated that the inhibition of energy metabolism by sodium azide down-regulates PS2 gene expression through modification of promoter activity. No one of the analyzed transcription factors, sensitive to redox status of the cell, could explain this effect. Azide effect on PS2 expression was completely inhibited by the addition of an antioxidant suggesting that the imbalance of the cellular redox homeostasis modulates the expression of this gene.

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Inhibition of energy metabolism down-regulates the Alzheimer related presenilin 2 gene

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Keywords

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