Neuroprotective Effects of Chaperonin Containing TCP1 Subunit 2 (CCT2) on Motor Neurons Following Oxidative or Ischemic Stress

Hyun Jung Kwon ^1,2, Hyunwoong Mun ³, Jae Keun Oh ³

¹Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Gangneung-Wonju National University, Gangneung, 25457, South Korea.
²Department of Biomedical Sciences, Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon, 24252, South Korea.
³Department of Neurosurgery, College of Medicine, Hallym University Sacred Heart Hospital, Hallym University, Anyang, 14068, South Korea.
⁴Department of Thoracic and Cardiovascular Surgery, Chuncheon Sacred Heart Hospital, College of Medicine, Hallym University, Chuncheon, 24253, South Korea.
⁵Department of Anatomy and Cell Biology, College of Veterinary Medicine, Research Institute for Veterinary Science, Seoul National University, Seoul, 08826, South Korea.
⁶Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Gangneung-Wonju National University, Gangneung, 25457, South Korea. kimdw@gwnu.ac.kr.
⁷Department of Neurosurgery, Kangnam Sacred Heart Hospital, College of Medicine, Hallym University, Seoul, 07441, South Korea. nsmsm@hallym.ac.kr.
⁸Research Institute for Complementary & Alternative Medicine, Hallym University, Chuncheon, 24253, South Korea. nsmsm@hallym.ac.kr.

⁰Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Gangneung-Wonju National University, Gangneung, 25457, South Korea.

Neurochemical Research +

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November 29, 2024

View abstract on PubMed

Summary

Tat-CCT2 fusion protein protects neurons from oxidative damage and spinal cord injury. This novel therapeutic agent reduces reactive oxygen species, DNA fragmentation, and inflammation, improving neurological function after ischemia.

Area Of Science

Neuroscience
Molecular Biology
Biochemistry

Background

Chaperonin containing TCP1 (CCT) is crucial for proteostasis, particularly CCT2's role in neurological disorders.
Limited research exists on CCT2's impact on spinal cord ischemic damage.
Neuronal death in neurological conditions highlights the need for protective strategies.

Purpose Of The Study

To investigate the neuroprotective effects of a cell-permeable Tat-CCT2 fusion protein.
To evaluate Tat-CCT2's efficacy against oxidative damage in vitro and ischemic injury in vivo.
To explore the underlying mechanisms of Tat-CCT2's protective action.

Main Methods

Synthesized a cell-permeable Tat-CCT2 fusion protein.
Assessed Tat-CCT2 delivery, localization, and degradation in NSC34 motoneuron-like cells.
Induced oxidative damage using H2O2 in vitro and ischemic injury in rabbit spinal cords.
Measured neuronal damage, reactive oxygen species, DNA fragmentation, neurological scores, cell survival, oxidative stress markers, and inflammatory cytokines.

Main Results

Tat-CCT2 efficiently entered NSC34 cells and rabbit spinal cords, with observed cytosolic localization and gradual degradation.
Tat-CCT2 significantly ameliorated H2O2-induced neuronal damage, reactive oxygen species, and DNA fragmentation in vitro.
In vivo, Tat-CCT2 treatment improved neurological scores, increased neuronal survival, and reduced oxidative stress, ferroptosis markers, and pro-inflammatory cytokines post-ischemia/reperfusion.
Tat-CCT2 also mitigated ischemia-induced microglial activation in the spinal cord.

Conclusions

Tat-CCT2 demonstrates significant neuroprotective effects against oxidative stress and ischemic injury in the spinal cord.
The fusion protein effectively penetrates target cells and tissues, offering a promising therapeutic avenue.
Tat-CCT2 mitigates neuronal damage by reducing oxidative stress, inflammation, and microglial activation, thereby improving functional recovery.

Keywords:

CCT2 Ferroptosis Inflammatory cytokine Ischemia Neuroprotection Oxidative damage