e6819fbf05bc82beb2046c702ccecb40 328648.pdf 3718e23aef2cbc0dcd210da9098bcdce9f07cd55 328648.pdf 58b8fbd515fe03d998e46766f79fba3fe476902df4dad59a5ad6f1e9995b47c7 328648.pdf Title: The NADPH Link between the Renin Angiotensin System and the Antioxidant Mechanisms in Dopaminergic Neurons Subject: The renin angiotensin system (RAS) has several components including signaling peptides, enzymes, and membrane receptors. The effort in characterizing this system in the periphery has led to the approval of a class of antihypertensives. Much less is known about RAS in the central nervous system. The production of RAS peptides and the expression of several RAS enzymes and receptors in dopaminergic neurons of the substantia nigra has raised expectations in the therapy of Parkinson’s disease, a neurodegenerative condition characterized by lack of dopamine in the striatum, the motor control region of the mammalian brain. On the one hand, dopamine production requires reducing power. On the other hand, reducing power is required by mechanisms involved in REDOX homeostasis. This review focuses on the potential role of RAS in the regulation of neuronal/glial expression of glucose-6-phosphate dehydrogenase, which produces the NADPH required for dopamine synthesis and for reactive oxygen species (ROS) detoxification. It is known that transgenic expression of the gene coding for glucose-6-phosphate dehydrogenase prevents the death of dopaminergic nigral neurons. Signaling via angiotensin II G protein-coupled receptors, AT1 or AT2, leads to the activation of protein kinase A and/or protein kinase C that in turn can regulate glucose-6- phosphate dehydrogenase activity, by Ser/Thr phosphorylation/dephosphorylation events. Long-term effects of AT1 or AT2 receptor activation may also impact on the concentration of the enzyme via activation of transcription factors that participate in the regulation of gene expression in neurons (or glia). Future research is needed to determine how the system can be pharmacologically manipulated to increase the availability of NADPH to neurons degenerating in Parkinson’s disease and to neuroprotective glia. Keywords: Parkinson’s disease; glucose-6-phosphate dehydrogenase; NADPH; substantia nigra; brain; angiotensin receptors; MAS receptors; glutathione; 6-phospho-gluconate dehydrogenase; neuromelanin Author: Rafael Franco, Joan Serrano-Marín, Gemma Navarro and Rafael Rivas-Santisteban Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Mon Oct 16 13:18:41 2023 CEST ModDate: Mon Oct 16 13:22:39 2023 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 14 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1247285 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- WLENKM+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 AQQNSY+VnURWPalladioL Type 1 Custom yes yes no 15 0 JEMXWC+URWPalladioL-Bold Type 1 Custom yes yes no 19 0 CRKARO+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 CUNAPY+URWPalladioL-Ital Type 1 Custom yes yes no 28 0 KUDXZB+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 46 0 IYELBM+CMSY10 Type 1 Builtin yes yes no 68 0 OOEGDA+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 79 0 OOEGDB+PalatinoLinotype CID TrueType Identity-H yes yes yes 82 0 OOEGDC+PalatinoLinotype TrueType WinAnsi yes yes no 88 0 OOEGDE+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 91 0 OOEGNB+PalatinoLinotype TrueType MacRoman yes yes no 94 0 OOEHCA+Arial CID TrueType Identity-H yes yes yes 97 0 LWLIVD+EURM10 Type 1 Builtin yes yes no 116 0 OOEGDA+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 127 0 OOEGDB+PalatinoLinotype CID TrueType Identity-H yes yes yes 130 0 OOEGDC+PalatinoLinotype TrueType WinAnsi yes yes no 136 0 OOEGDE+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 139 0 OOEGNB+PalatinoLinotype TrueType MacRoman yes yes no 142 0 OOEIMI+PalatinoLinotype,BoldItalic TrueType WinAnsi yes yes no 162 0 OOEGDA+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 165 0 OOEGDB+PalatinoLinotype CID TrueType Identity-H yes yes yes 168 0 OOEGDC+PalatinoLinotype TrueType WinAnsi yes yes no 174 0 OOEGDE+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 177 0 OOEGNB+PalatinoLinotype TrueType MacRoman yes yes no 180 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2026-06-23 04:14:44 CEST RepresentationInformation: 328648.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2026-06-22 13:12:29 CEST Size: 1247285 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 445 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Components of the RAS System Destination: section.2 Item: Title: RAS in the CNS Destination: section.3 Item: Title: NADPH Is Needed for Keeping REDOX Homeostasis in the CNS Destination: section.4 Children: Item: Title: Transgenic Expression of the Gene Coding for Glucose-6-Phosphate Dehydrogenase Prevents Nigral Neurodegeneration Destination: subsection.4.1 Item: Title: Role of the Pentose Phosphate Pathway in the CNS: Evidence from Patient Samples and from Preclinical Studies in Animal Models of Neurodegeneration Destination: subsection.4.2 Item: Title: Peripheral RAS and Glucose Availability to the Brain Destination: section.5 Item: Title: Regulation by RAS of the Expression of Genes Coding for Protein Needed in Antioxidant Routes Destination: section.6 Children: Item: Title: Effect of RAS-Targeted Anti-Hypertensive Drugs Destination: subsection.6.1 Item: Title: Evidence of Angiotensin II Effects on AT1 and AT2 Receptors Using AT1R KO Mice Destination: subsection.6.2 Item: Title: Expression of G6PDH in Cells Isolated from Patients with Preeclampsia Destination: subsection.6.3 Item: Title: Assessing the Potential of RAS to Regulate NADPH Production Destination: section.7 Item: Title: Conclusions Destination: section.8 Item: Title: References Destination: section.9 Info: Title: The NADPH Link between the Renin Angiotensin System and the Antioxidant Mechanisms in Dopaminergic Neurons Author: Rafael Franco, Joan Serrano-Marín, Gemma Navarro and Rafael Rivas-Santisteban Subject: The renin angiotensin system (RAS) has several components including signaling peptides, enzymes, and membrane receptors. The effort in characterizing this system in the periphery has led to the approval of a class of antihypertensives. Much less is known about RAS in the central nervous system. The production of RAS peptides and the expression of several RAS enzymes and receptors in dopaminergic neurons of the substantia nigra has raised expectations in the therapy of Parkinson’s disease, a neurodegenerative condition characterized by lack of dopamine in the striatum, the motor control region of the mammalian brain. On the one hand, dopamine production requires reducing power. On the other hand, reducing power is required by mechanisms involved in REDOX homeostasis. This review focuses on the potential role of RAS in the regulation of neuronal/glial expression of glucose-6-phosphate dehydrogenase, which produces the NADPH required for dopamine synthesis and for reactive oxygen species (ROS) detoxification. It is known that transgenic expression of the gene coding for glucose-6-phosphate dehydrogenase prevents the death of dopaminergic nigral neurons. Signaling via angiotensin II G protein-coupled receptors, AT1 or AT2, leads to the activation of protein kinase A and/or protein kinase C that in turn can regulate glucose-6- phosphate dehydrogenase activity, by Ser/Thr phosphorylation/dephosphorylation events. Long-term effects of AT1 or AT2 receptor activation may also impact on the concentration of the enzyme via activation of transcription factors that participate in the regulation of gene expression in neurons (or glia). Future research is needed to determine how the system can be pharmacologically manipulated to increase the availability of NADPH to neurons degenerating in Parkinson’s disease and to neuroprotective glia. Keywords: Parkinson’s disease; glucose-6-phosphate dehydrogenase; NADPH; substantia nigra; brain; angiotensin receptors; MAS receptors; glutathione; 6-phospho-gluconate dehydrogenase; neuromelanin Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Mon Oct 16 13:18:41 CEST 2023 ModDate: Mon Oct 16 13:22:39 CEST 2023 ID: 0x4699a88db67932a8f52c7987aa879505, 0x4699a88db67932a8f52c7987aa879505 Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: JEMXWC+URWPalladioL-Bold FontSubset: true FirstChar: 3 LastChar: 134 FontDescriptor: FontName: JEMXWC+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: IYELBM+CMSY10 FontSubset: true FirstChar: 0 LastChar: 15 FontDescriptor: FontName: IYELBM+CMSY10 Flags: Symbolic FontBBox: -29, -960, 1116, 775 FontFile: true Font: BaseFont: LWLIVD+EURM10 FontSubset: true FirstChar: 12 LastChar: 12 FontDescriptor: FontName: LWLIVD+EURM10 Flags: 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