Chaperone-Mediated Autophagy after Spinal Cord Injury

Kyoichi Handa, Haruo Kanno, Michiharu Matsuda, Takehiro Sugaya, Taishi Murakami, Maria Prudnikova, Hiroshi Ozawa, Eiji Itoi

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Autophagy is the degradation process of dysfunctional intracellular components and has a crucial function in various human diseases. There are three different types of autophagy: macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA). CMA is a major route for the elimination of cellular aberrant proteins and can provide a cytoprotective effect. The present study investigated the expression of lysosome-associated membrane protein type 2A (LAMP2A), which is the hallmark of CMA activity, in damaged neural tissue after spinal cord injury (SCI) in mice. The number of LAMP2A-expressing cells was significantly increased at the lesion following SCI. The increased number of LAMP2A-positive cells was observed from 24 h and peaked at 3 days after injury. A western blot analysis confirmed that the level of LAMP2A protein was significantly increased in the injured spinal cord compared with the uninjured cord. On double staining for LAMP2A and different neural cell type markers, the increased expression of LAMP2A was observed in neurons, astrocytes, oligodendrocytes, and microglia/macrophages following injury. An electron microscopic analysis showed that secondary lysosomes were increased in damaged neurons at the lesion site. Immunoelectron microscopy revealed that the gold particles with anti-LAMP2A antibody were frequently localized at the secondary lysosomes in the injured site. These findings indicated that CMA was clearly activated in damaged neural tissue after SCI. The activation of CMA may contribute to the elimination of intracellular aberrant proteins and exert a neuroprotective effect following SCI.

Original languageEnglish
Pages (from-to)1687-1695
Number of pages9
JournalJournal of Neurotrauma
Volume37
Issue number15
DOIs
Publication statusPublished - 2020 Aug 1

Keywords

  • HSC70
  • LAMP2A
  • chaperone-mediated autophagy
  • lysosome
  • spinal cord injury

ASJC Scopus subject areas

  • Clinical Neurology

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