Chronic Caffeine Treatment Protects Against α-Synucleinopathy by Reestablishing Autophagy Activity in the Mouse Striatum

Despite converging epidemiological evidence for the inverse relationship of regular caffeine consumption and risk of developing Parkinson's disease (PD) with animal studies demonstrating protective effect of caffeine in various neurotoxin models of PD, whether caffeine can protect against mutan...

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Published in:Frontiers in neuroscience 2018-05, Vol.12, p.301-301
Main Authors: Luan, Yanan, Ren, Xiangpeng, Zheng, Wu, Zeng, Zhenhai, Guo, Yingzi, Hou, Zhidong, Guo, Wei, Chen, Xingjun, Li, Fei, Chen, Jiang-Fan
Format: Article
Language:English
Subjects:
Animal cognition
Apoptosis
Astrocytes
Autophagy
Axons
Caffeine
Cell death
Cortex
Dopamine receptors
Epidemiology
Fibrils
Laboratory animals
Lewy bodies
macroautophagy
Medulla oblongata
Mesencephalon
Microglia
Microtubule-associated protein 1
Movement disorders
Neostriatum
Nervous system
Neurodegeneration
Neurodegenerative diseases
Neurons
Neuroscience
Neurotoxicity
Parkinson's disease
Pathogenesis
Pathology
Phagocytosis
Studies
Synuclein
α-synuclein
α-synucleinopathy
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Summary:Despite converging epidemiological evidence for the inverse relationship of regular caffeine consumption and risk of developing Parkinson's disease (PD) with animal studies demonstrating protective effect of caffeine in various neurotoxin models of PD, whether caffeine can protect against mutant α-synuclein (α-Syn) A53T-induced neurotoxicity in intact animals has not been examined. Here, we determined the effect of chronic caffeine treatment using the α-Syn fibril model of PD by intra-striatal injection of preformed A53T α-Syn fibrils. We demonstrated that chronic caffeine treatment blunted a cascade of pathological events leading to α-synucleinopathy, including pSer129α-Syn-rich aggregates, apoptotic neuronal cell death, microglia, and astroglia reactivation. Importantly, chronic caffeine treatment did not affect autophagy processes in the normal striatum, but selectively reversed α-Syn-induced defects in macroautophagy (by enhancing microtubule-associated protein 1 light chain 3, and reducing the receptor protein sequestosome 1, SQSTM1/p62) and chaperone-mediated autophagy (CMA, by enhancing LAMP2A). These findings support that caffeine-a strongly protective environment factor as suggested by epidemiological evidence-may represent a novel pharmacological therapy for PD by targeting autophagy pathway.
ISSN:1662-4548
1662-453X
1662-453X
DOI:10.3389/fnins.2018.00301