Microglia-Mediated Neuroinflammation and Neurotrophic Factor-Induced Protection in the MPTP Mouse Model of Parkinson's Disease-Lessons from Transgenic Mice

International Journal of Molecular Sciences
Venissa MachadoBjörn Spittau

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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Citations

Dec 14, 2016·Annual Review of Physiology·Susanne A WolfHelmut Kettenmann
Nov 6, 2018·The Journal of Experimental Medicine·Reem Abdel-HaqSarkis K Mazmanian
Oct 3, 2018·Nature Communications·Tanja ZöllerBjörn Spittau
Dec 7, 2018·Frontiers in Cellular Neuroscience·Khadija TayaraRocío M de Pablos
Mar 25, 2017·Frontiers in Molecular Neuroscience·Laura HühnerBjörn Spittau
May 6, 2019·Mayo Clinic Proceedings·Nathan P StaffWolfgang Singer
Apr 4, 2021·International Journal of Molecular Sciences·Mehdi EshraghiSaeid Ghavami
May 14, 2021·Frontiers in Genetics·Adrienne R HendersonTravis Dunckley

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Methods Mentioned

BETA
ICE
Transgenic
transfection

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