2. Academic Validation
  3. SELENOK-dependent CD36 palmitoylation regulates microglial functions and Aβ phagocytosis

SELENOK-dependent CD36 palmitoylation regulates microglial functions and Aβ phagocytosis

  • Redox Biol. 2024 Apr:70:103064. doi: 10.1016/j.redox.2024.103064.
Pei Ouyang 1,  Zhiyu Cai 2,  Jiaying Peng 2,  Shujing Lin 2,  Xiaochun Chen 2,  Changbin Chen 2,  Ziqi Feng 2,  Lin Wang 3,  Guoli Song 4,  Zhonghao Zhang 5
Affiliations

Affiliations

  • 1 Shenzhen Key Laboratory of Marine Bioresources and Ecology, Brain Disease and Big Data Research Institute, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, China; Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, China.
  • 2 Shenzhen Key Laboratory of Marine Bioresources and Ecology, Brain Disease and Big Data Research Institute, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, China.
  • 3 College of Biology and Food Engineering, Anyang Institute of Technology, Anyang, China.
  • 4 Shenzhen Key Laboratory of Marine Bioresources and Ecology, Brain Disease and Big Data Research Institute, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, China; Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, China. Electronic address: [email protected].
  • 5 Shenzhen Key Laboratory of Marine Bioresources and Ecology, Brain Disease and Big Data Research Institute, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, China; Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, China. Electronic address: [email protected].
PMID: 38320455 DOI: 10.1016/j.redox.2024.103064
Abstract

Amyloid-beta (Aβ) is a key factor in the onset and progression of Alzheimer's disease (AD). Selenium (Se) compounds show promise in AD treatment. Here, we revealed that selenoprotein K (SELENOK), a selenoprotein involved in immune regulation and potentially related to AD pathology, plays a critical role in microglial immune response, migration, and phagocytosis. In vivo and in vitro studies corroborated that SELENOK deficiency inhibits microglial Aβ phagocytosis, exacerbating cognitive deficits in 5xFAD mice, which are reversed by SELENOK overexpression. Mechanistically, SELENOK is involved in CD36 palmitoylation through DHHC6, regulating CD36 localization to microglial plasma membranes and thus impacting Aβ phagocytosis. CD36 palmitoylation was reduced in the brains of patients and mice with AD. Se supplementation promoted SELENOK expression and CD36 palmitoylation, enhancing microglial Aβ phagocytosis and mitigating AD progression. We have identified the regulatory mechanisms from Se-dependent selenoproteins to Aβ pathology, providing novel insights into potential therapeutic strategies involving Se and selenoproteins.

Keywords

Alzheimer's disease; Amyloid-beta; CD36 palmitoylation; Microglial phagocytosis; Selenoprotein K.

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