1. Melatonin regulates mitochondrial dynamics and alleviates neuron damage in prion diseases.
- Author
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Zhang X, Zhao D, Wu W, Ali Shah SZ, Lai M, Yang D, Li J, Guan Z, Li W, Gao H, Zhao H, Zhou X, and Yang L
- Subjects
- Animals, Cell Line, Tumor, Dynamins genetics, Dynamins metabolism, GTP Phosphohydrolases genetics, GTP Phosphohydrolases metabolism, Membrane Potential, Mitochondrial drug effects, Neurons pathology, Neuroprotective Agents pharmacology, Prion Diseases drug therapy, Prion Diseases pathology, Reactive Oxygen Species metabolism, Apoptosis drug effects, Melatonin pharmacology, Mitochondrial Dynamics drug effects, Neurons drug effects
- Abstract
Prion diseases are neurodegenerative diseases associated with neuron damage and behavioral disorders in animals and humans. Melatonin is a potent antioxidant and is used to treat a variety of diseases. We investigated the neuroprotective effect of melatonin on prion-induced damage in N2a cells. N2a cells were pretreated with 10 μM melatonin for 1 hour followed by incubation with 100 μM PrP
106-126 for 24 hours. Melatonin markedly alleviated PrP106-126 -induced apoptosis of N2a cells, and inhibited PrP106-126 -induced mitochondrial abnormality and dysfunction, including mitochondrial fragmentation and overproduction of reactive oxygen species (ROS), suppression of ATP, reduced mitochondrial membrane potential (MMP), and altered mitochondrial dynamic proteins dynamin-related protein 1 (DRP1) and optic atrophy protein 1 (OPA1). Our findings identify that pretreatment with melatonin prevents the deleterious effects of PrPSc on mitochondrial function and dynamics, protects synapses and alleviates neuron damage. Melatonin could be a novel and effective medication in the therapy of prion diseases.- Published
- 2020
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