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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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).”
From LC3-Associated Endocytosis Facilitates β-Amyloid Clearance and Mitigates Neurodegeneration in Murine Alzheimer’s Disease (2019) · cites this paper as Machado et al., 2016
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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)
- PMC
- PMC4783885
- 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
- gold
- doi.org
- Licence
- 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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