2. Academic Validation
  3. Optineurin regulates motor and learning behaviors by affecting dopaminergic neuron survival in mice

Optineurin regulates motor and learning behaviors by affecting dopaminergic neuron survival in mice

  • Exp Neurol. 2024 Oct 18:383:115007. doi: 10.1016/j.expneurol.2024.115007.
Xianfei Yang 1,  Ruoling Zheng 2,  Hongyao Zhang 1,  Zixian Ou 1,  Sha Wan 3,  Dongfeng Lin 4,  Jianguo Yan 5,  Mingyue Jin 1,  Jie Tan 6
Affiliations

Affiliations

  • 1 Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin Medical University, Guilin 541199, China.
  • 2 Shantou Longhu People's Hospital, Shantou 515041, China.
  • 3 Department of Anatomy, College of Basic Medicine, Guilin Medical University, Guilin 541199, China.
  • 4 Shantou University Mental Health Center, Shantou University, Shantou 515063, China.
  • 5 Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin Medical University, Guilin 541199, China; Department of Physiology, College of Basic Medicine, Guilin Medical University, Guilin 541199, China.
  • 6 Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin Medical University, Guilin 541199, China; Department of Physiology, College of Basic Medicine, Guilin Medical University, Guilin 541199, China; Clinical Research Center for Neurological Diseases of Guangxi Province, The Affiliated Hospital of Guilin Medical University, Guilin 541001, China. Electronic address: jietan03@outlook.com.
PMID: 39428042 DOI: 10.1016/j.expneurol.2024.115007
Abstract

Optineurin (OPTN) is an Autophagy receptor that participates in the degradation of damaged mitochondria, protein aggregates, and invading pathogens. OPTN is closely related to various types of neurodegenerative diseases. However, the role of OPTN in the central nervous system is unclear. Here, we found that OPTN dysregulation in the compact part of substantia nigra (SNc) led to motor and learning deficits in animal models. Knockdown of OPTN increased total and phosphorylated α-synuclein levels which induced microglial activation and dopaminergic neuronal loss in the SNc. Overexpression of OPTN can't reverse the motor and learning phenotypes. Mechanistic analysis revealed that upregulation of OPTN increased α-synuclein phosphorylation independent of its Autophagy receptor activity, which further resulted in microglial activation and dopaminergic neuronal loss similar to OPTN downregulation. Our study uncovers the crucial role of OPTN in maintaining dopaminergic neuron survival and motor and learning functions which are disrupted in PD patients.

Keywords

Autophagy; Dopaminergic neurons; Neurodegenerative diseases; OPTN.

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