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Cited by 63Parkinson's Disease Mechanisms and TreatmentsNeuroinflammation and Neurodegeneration MechanismsNuclear Receptors and Signaling

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

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Durrenberger, Pascal. F., Grünblatt, Edna, Fernando, Francesca S., Monoranu, Camelia Maria, Evans, Jordan, Riederer, Peter, Reynolds, Richard, Dexter, David T.·2012·Parkinson's Disease
DOI 10.1155/2012/214714PMC PMC3324922
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Abstract

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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  • Expression and function of P2X7R are enhanced in PD patients.

    “It has been shown that the expression and function of P2X7R are enhanced in PD patients.383”

    From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [383]

    The Discussion (§4.2; page not supplied) reports increased P2RX7 mRNA in the substantia nigra of PD patients, confirmed by RT-qPCR. It describes what the receptor does when activated, but does not show that P2X7R function is enhanced in those patients. (LLM, conf=0.88)

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Authors
Durrenberger, P. F., Grünblatt, E., Fernando, F. S., Monoranu, C. M., Evans, J., Riederer, P., Reynolds, R., & Dexter, D. T.
Affiliations
  • Hammersmith Hospital (GB)
  • University of Zurich (CH)
  • University of Würzburg (DE)
  • Universitätsklinikum Würzburg (DE)
Corresponding author
Dexter, David T.
ORCID
Venue
Parkinson's Disease
Publisher
Wiley
Published
2012
Volume
2012
Pages
1-16
ISSN
  • 2042-0080 (ISSN-L)
  • 2090-8083
DOI
10.1155/2012/214714
PMC
PMC3324922
OpenAlex
W2073723516
Cited by
63
References
8
Citations by year
2026: 2 · 2025: 6 · 2024: 3 · 2023: 8 · 2021: 8 · 2020: 2 · 2019: 4 · 2018: 5 · 2017: 4 · 2016: 6 · 2015: 3 · 2014: 5 · 2013: 3 · 2012: 4
FWCI
3.14
Type
journal article
Language
en
Open access
Licence
Locations
  • Parkinson s Disease (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Online Publication Service of Würzburg University (Würzburg University) (submittedVersion, cc-by)
  • Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by)
  • Zurich Open Repository and Archive (University of Zurich)
Funders
  • Parkinson’s UK
  • European Commission
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
Keywords
neuroinflammation, substantia nigra, alpha-synuclein, ALDH1A1, dopamine metabolism, oxidative stress, neuronal cell death, microglial activation, P2X7 receptor, NOS3, nitric oxide synthase, angiogenesis, astrocytes, extracellular ATP, inflammatory cytokines, neuroprotection

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