Research Paper Volume 12, Issue 11 pp 11139—11151

Melatonin regulates mitochondrial dynamics and alleviates neuron damage in prion diseases

Xixi Zhang1, , Deming Zhao1, , Wei Wu1, , Syed Zahid Ali Shah2, , Mengyu Lai1, , Dongming Yang1, , Jie Li1, , Zhiling Guan1, , Wen Li1, , Hongli Gao1, , Huafen Zhao1, , Xiangmei Zhou1, , Lifeng Yang1, ,

  • 1 Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China
  • 2 Department of Pathology, Faculty of Veterinary Sciences, Cholistan University of Veterinary and Animal Sciences, Bahawalpur 63100, Pakistan

Received: December 24, 2019       Accepted: April 17, 2020       Published: June 10, 2020
How to Cite

Copyright © 2020 Zhang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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 PrP106-126 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.


TSE: Transmissible spongiform encephalopathy; ROS: reactive oxygen species; MMP: mitochondrial membrane potential; PSD95: Postsynaptic density protein-95; AR: aspect ratio; DRP1: dynamin-related protein 1; OPA1: optic atrophy protein 1; MFN1/2: fusion protein mitofusin-1/2; PD: Parkinson's disease; HD: Huntington's disease; ALS: Amyotrophic lateral sclerosis; MEL: melatonin.