Rifampicin and Its Derivative Rifampicin Quinone Reduce Microglial Inflammatory Responses and Neurodegeneration Induced In Vitro by α-Synuclein Fibrillary Aggregates
Abstract
:1. Introduction
2. Materials and Methods
2.1. Preparation of α-synuclein
2.2. Transmission Electron Microscopy
2.3. Cell Culture Protocols
2.3.1. Microglial Cell Isolation
2.3.2. Microglial Cell Stimulation and Treatments
2.3.3. Primary Cortical Neuron Cultures
2.3.4. Neurotoxicity Assays
2.3.5. Microglial-Conditioned Media Preparation
2.4. Protein Detection by Immunofluorescence
2.5. Western Blot Analysis
2.6. NADPH Oxidase Activity
2.7. Statistical Analysis
3. Results
3.1. α-Synuclein Fibrils Induce Pro-Inflammatory Cytokine Release in Microglial Cell Cultures
3.2. Rifampicin and Rifampicin Quinone Prevent Microglial Activation Induced by α-Synuclein Fibrils
3.3. Rifampicin and Rifampicin Quinone Prevent TLR2- and P2X7-Dependent Microglial Activation
3.4. Inhibitory Effect of Rif and RifQ on αSf-Induced PI3K/AKT Activity
3.5. Rifampicin and Rifampicin Quinone Prevent Reactive Oxygen Species Production in Microglial Cells Activated by αSf
3.6. Rifampicin Quinone Protects Cortical Neurons Against Death Caused by αSf-Induced Microglial Activation
4. Discussion
4.1. Fibrillary Aggregates of αS are the Most Inflammogenic Forms of αS for Microglial Cells
4.2. RifQ is More Efficient than Rif in Reducing αSf-Induced Microglial Cell Activation
4.3. Rif and RifQ Inhibit an Activation Process Mediated by TLR2 and P2X7 Receptors
4.4. Rifampicin and Rifampicin Quinone act as Inhibitors of PI3K/AKT-Dependent Signaling
4.5. Rifampicin Quinone Provides Neuroprotection through its Anti-Inflammatory Activity
Author Contributions
Funding
Conflicts of Interest
References
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Acuña, L.; Hamadat, S.; Corbalán, N.S.; González-Lizárraga, F.; dos-Santos-Pereira, M.; Rocca, J.; Sepúlveda Díaz, J.; Del-Bel, E.; Papy-García, D.; Chehín, R.N.; et al. Rifampicin and Its Derivative Rifampicin Quinone Reduce Microglial Inflammatory Responses and Neurodegeneration Induced In Vitro by α-Synuclein Fibrillary Aggregates. Cells 2019, 8, 776. https://0-doi-org.brum.beds.ac.uk/10.3390/cells8080776
Acuña L, Hamadat S, Corbalán NS, González-Lizárraga F, dos-Santos-Pereira M, Rocca J, Sepúlveda Díaz J, Del-Bel E, Papy-García D, Chehín RN, et al. Rifampicin and Its Derivative Rifampicin Quinone Reduce Microglial Inflammatory Responses and Neurodegeneration Induced In Vitro by α-Synuclein Fibrillary Aggregates. Cells. 2019; 8(8):776. https://0-doi-org.brum.beds.ac.uk/10.3390/cells8080776
Chicago/Turabian StyleAcuña, Leonardo, Sabah Hamadat, Natalia S. Corbalán, Florencia González-Lizárraga, Mauricio dos-Santos-Pereira, Jérémy Rocca, Julia Sepúlveda Díaz, Elaine Del-Bel, Dulce Papy-García, Rosana N. Chehín, and et al. 2019. "Rifampicin and Its Derivative Rifampicin Quinone Reduce Microglial Inflammatory Responses and Neurodegeneration Induced In Vitro by α-Synuclein Fibrillary Aggregates" Cells 8, no. 8: 776. https://0-doi-org.brum.beds.ac.uk/10.3390/cells8080776