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Inflammatory Pathways in Parkinson's Disease; A BNE Microarray Study

The aetiology of Parkinson's disease (PD) is yet to be fully understood but it is becoming more and more evident that neuronal cell death may be multifactorial in essence. The main focus of PD research is to better understand substantia nigra homeostasis disruption, particularly in relation to...

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Autores principales: Durrenberger, Pascal. F., Grünblatt, Edna, Fernando, Francesca S., Monoranu, Camelia Maria, Evans, Jordan, Riederer, Peter, Reynolds, Richard, Dexter, David T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3324922/
https://www.ncbi.nlm.nih.gov/pubmed/22548201
http://dx.doi.org/10.1155/2012/214714
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author Durrenberger, Pascal. F.
Grünblatt, Edna
Fernando, Francesca S.
Monoranu, Camelia Maria
Evans, Jordan
Riederer, Peter
Reynolds, Richard
Dexter, David T.
author_facet Durrenberger, Pascal. F.
Grünblatt, Edna
Fernando, Francesca S.
Monoranu, Camelia Maria
Evans, Jordan
Riederer, Peter
Reynolds, Richard
Dexter, David T.
author_sort Durrenberger, Pascal. F.
collection PubMed
description The aetiology of Parkinson's disease (PD) is yet to be fully understood but it is becoming more and more evident that neuronal cell death may be multifactorial in essence. The main focus of PD research is to better understand substantia nigra homeostasis disruption, particularly in relation to the wide-spread deposition of the aberrant protein α-synuclein. Microarray technology contributed towards PD research with several studies to date and one gene, ALDH1A1 (Aldehyde dehydrogenase 1 family, member A1), consistently reappeared across studies including the present study, highlighting dopamine (DA) metabolism dysfunction resulting in oxidative stress and most probably leading to neuronal cell death. Neuronal cell death leads to increased inflammation through the activation of astrocytes and microglia. Using our dataset, we aimed to isolate some of these pathways so to offer potential novel neuroprotective therapeutic avenues. To that effect our study has focused on the upregulation of P2X7 (purinergic receptor P2X, ligand-gated ion channel, 7) receptor pathway (microglial activation) and on the NOS3 (nitric oxide synthase 3) pathway (angiogenesis). In summary, although the exact initiator of striatal DA neuronal cell death remains to be determined, based on our analysis, this event does not remain without consequence. Extracellular ATP and reactive astrocytes appear to be responsible for the activation of microglia which in turn release proinflammatory cytokines contributing further to the parkinsonian condition. In addition to tackling oxidative stress pathways we also suggest to reduce microglial and endothelial activation to support neuronal outgrowth.
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spelling pubmed-33249222012-04-30 Inflammatory Pathways in Parkinson's Disease; A BNE Microarray Study Durrenberger, Pascal. F. Grünblatt, Edna Fernando, Francesca S. Monoranu, Camelia Maria Evans, Jordan Riederer, Peter Reynolds, Richard Dexter, David T. Parkinsons Dis Research Article The aetiology of Parkinson's disease (PD) is yet to be fully understood but it is becoming more and more evident that neuronal cell death may be multifactorial in essence. The main focus of PD research is to better understand substantia nigra homeostasis disruption, particularly in relation to the wide-spread deposition of the aberrant protein α-synuclein. Microarray technology contributed towards PD research with several studies to date and one gene, ALDH1A1 (Aldehyde dehydrogenase 1 family, member A1), consistently reappeared across studies including the present study, highlighting dopamine (DA) metabolism dysfunction resulting in oxidative stress and most probably leading to neuronal cell death. Neuronal cell death leads to increased inflammation through the activation of astrocytes and microglia. Using our dataset, we aimed to isolate some of these pathways so to offer potential novel neuroprotective therapeutic avenues. To that effect our study has focused on the upregulation of P2X7 (purinergic receptor P2X, ligand-gated ion channel, 7) receptor pathway (microglial activation) and on the NOS3 (nitric oxide synthase 3) pathway (angiogenesis). In summary, although the exact initiator of striatal DA neuronal cell death remains to be determined, based on our analysis, this event does not remain without consequence. Extracellular ATP and reactive astrocytes appear to be responsible for the activation of microglia which in turn release proinflammatory cytokines contributing further to the parkinsonian condition. In addition to tackling oxidative stress pathways we also suggest to reduce microglial and endothelial activation to support neuronal outgrowth. Hindawi Publishing Corporation 2012 2012-04-02 /pmc/articles/PMC3324922/ /pubmed/22548201 http://dx.doi.org/10.1155/2012/214714 Text en Copyright © 2012 Pascal. F. Durrenberger et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Durrenberger, Pascal. F.
Grünblatt, Edna
Fernando, Francesca S.
Monoranu, Camelia Maria
Evans, Jordan
Riederer, Peter
Reynolds, Richard
Dexter, David T.
Inflammatory Pathways in Parkinson's Disease; A BNE Microarray Study
title Inflammatory Pathways in Parkinson's Disease; A BNE Microarray Study
title_full Inflammatory Pathways in Parkinson's Disease; A BNE Microarray Study
title_fullStr Inflammatory Pathways in Parkinson's Disease; A BNE Microarray Study
title_full_unstemmed Inflammatory Pathways in Parkinson's Disease; A BNE Microarray Study
title_short Inflammatory Pathways in Parkinson's Disease; A BNE Microarray Study
title_sort inflammatory pathways in parkinson's disease; a bne microarray study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3324922/
https://www.ncbi.nlm.nih.gov/pubmed/22548201
http://dx.doi.org/10.1155/2012/214714
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