Cited by 76Neuroinflammation and Neurodegeneration MechanismsParkinson's Disease Mechanisms and TreatmentsNuclear Receptors and Signaling

Microglia-mediated neuroinflammation and neurotrophic factor-induced protection in the MPTP mouse model of parkinson’s disease-lessons from transgenic mice

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Machado, Venissa, Zöller, Tanja, Attaai, Abdelraheim, Spittau, Björn·2016·International Journal of Molecular Sciences

Abstract

Parkinson's disease (PD) is a neurodegenerative disease characterised by histopathological and biochemical manifestations such as loss of midbrain dopaminergic (DA) neurons and decrease in dopamine levels accompanied by a concomitant neuroinflammatory response in the affected brain regions. Over the past decades, the use of toxin-based animal models has been crucial to elucidate disease pathophysiology, and to develop therapeutic approaches aimed to alleviate its motor symptoms. Analyses of transgenic mice deficient for cytokines, chemokine as well as neurotrophic factors and their respective receptors in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD have broadened the current knowledge of neuroinflammation and neurotrophic support. Here, we provide a comprehensive review that summarises the contribution of microglia-mediated neuroinflammation in MPTP-induced neurodegeneration. Moreover, we highlight the contribution of neurotrophic factors as endogenous and/or exogenous molecules to slow the progression of midbrain dopaminergic (mDA) neurons and further discuss the potential of combined therapeutic approaches employing neuroinflammation modifying agents and neurotrophic factors.

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  • Microglia are the principal mediators of inflammation in response to Aβ accumulation, and their contribution to neuroinflammation is highly correlated with progression of neurodegeneration and synaptic dysfunction, particularly in Alzheimer's disease.

    “Microglia are the principal mediators of inflammation in response to Aβ accumulation (Machado et al., 2016; Perry and Holmes, 2014; Wang et al., 2015a), and their contribution to neuroinflammation is highly correlated to the progression of neurodegeneration and synaptic dysfunction, particularly with respect to Alzheimer’s disease (AD).”

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Authors
Machado, V., Zöller, T., Attaai, A., & Spittau, B.
Affiliations
University of Freiburg (DE)
Corresponding author
Spittau, Björn
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2016-01-26
Volume
17
Issue
2
Pages
151
ISSN
1422-0067 (ISSN-L)
OpenAlex
W2253007662
Cited by
76
References
137
Citations by year
2026: 1 · 2025: 8 · 2024: 13 · 2023: 6 · 2022: 5 · 2021: 8 · 2020: 6 · 2019: 7 · 2018: 11 · 2017: 8 · 2016: 3
FWCI
0.85
Type
journal article
Language
en
Open access
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • FreiDok plus (Universitätsbibliothek Freiburg) (submittedVersion)
Funders
Deutsche Forschungsgemeinschaft (SP 1555/2-1)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
Keywords
Parkinson's disease, microglia, neuroinflammation, neurotrophic factors, MPTP mouse model, midbrain dopaminergic neurons, neurodegeneration, transgenic mice, cytokines, chemokines, neurotrophic factor receptors, combination therapy
MeSH terms
Animals, Disease Models, Animal, Humans, Mice, Transgenic, Nerve Growth Factors, Parkinson Disease, Receptors, Nerve Growth Factor, Microglia, MPTP Poisoning, Mice

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