Chaperone-Mediated Autophagy after Spinal Cord Injury

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

doi:10.1089/neu.2019.6820

Cited by 12 publications

(11 citation statements)

References 44 publications

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“…The function of CMA is presumed to be restricted to mammals and birds [ 22 ], although other autophagic pathways are conserved from yeast to mammals. Importantly, CMA activity has been detected in many different mammalian cell types, including fibroblasts [ 23 ], hepatocytes [ 24 ], astrocytes [ 18 ], primary neurons [ 25 ], macrophages [ 26 ], dendritic cells [ 26 ], T-cells [ 27 ], retinal cells [ 28 ], and a large array of cancer cells of different origins [ 13 ]. Furthermore, CMA studies have been performed with lysosomes isolated from the liver [ 29 ], spleen [ 30 ], different brain regions [ 25 ], and kidneys [ 31 ].…”

Section: General Characteristics Of Cmamentioning

confidence: 99%

“…Many previous studies have provided experimental evidence that autophagy is an essential cytoprotective pathway for reducing secondary neural tissue damage and functional impairment after SCI [ 99 , 109 , 110 , 111 ]. We previously reported that LAMP2A protein expression was significantly upregulated in damaged neural tissue after SCI in mice [ 18 ]. The expression of LAMP2A was increased in various neural cells, such as neurons, astrocytes, oligodendrocytes, and microglia, in the injured spinal cord [ 18 ].…”

Section: Acute Neurological Insults and Cmamentioning

confidence: 99%

“…We previously reported that LAMP2A protein expression was significantly upregulated in damaged neural tissue after SCI in mice [ 18 ]. The expression of LAMP2A was increased in various neural cells, such as neurons, astrocytes, oligodendrocytes, and microglia, in the injured spinal cord [ 18 ]. These results indicated that CMA was activated in damaged neural tissue following SCI.…”

Section: Acute Neurological Insults and Cmamentioning

confidence: 99%

“…Conversely, it has been also reported that CMA activity is upregulated in damaged neural tissue after traumatic brain injury (TBI) [ 16 ] and cerebral ischemia [ 17 ], suggesting the cytoprotective role of CMA against acute brain damage. In addition, a previous study showed that CMA activity is promoted in various neural cells following spinal cord injury (SCI) [ 18 ]. Therefore, CMA may play an important role in neuroprotective mechanisms following acute CNS injury.…”

Section: Introductionmentioning

confidence: 99%

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Chaperone-Mediated Autophagy in Neurodegenerative Diseases and Acute Neurological Insults in the Central Nervous System

Kanno

Handa

Murakami

et al. 2022

Cells

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Autophagy is an important function that mediates the degradation of intracellular proteins and organelles. Chaperone-mediated autophagy (CMA) degrades selected proteins and has a crucial role in cellular proteostasis under various physiological and pathological conditions. CMA dysfunction leads to the accumulation of toxic protein aggregates in the central nervous system (CNS) and is involved in the pathogenic process of neurodegenerative diseases, including Parkinson’s disease and Alzheimer’s disease. Previous studies have suggested that the activation of CMA to degrade aberrant proteins can provide a neuroprotective effect in the CNS. Recent studies have shown that CMA activity is upregulated in damaged neural tissue following acute neurological insults, such as cerebral infarction, traumatic brain injury, and spinal cord injury. It has been also suggested that various protein degradation mechanisms are important for removing toxic aberrant proteins associated with secondary damage after acute neurological insults in the CNS. Therefore, enhancing the CMA pathway may induce neuroprotective effects not only in neurogenerative diseases but also in acute neurological insults. We herein review current knowledge concerning the biological mechanisms involved in CMA and highlight the role of CMA in neurodegenerative diseases and acute neurological insults. We also discuss the possibility of developing CMA-targeted therapeutic strategies for effective treatments.

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Section: General Characteristics Of Cmamentioning

confidence: 99%

Section: Acute Neurological Insults and Cmamentioning

confidence: 99%

Section: Acute Neurological Insults and Cmamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Chaperone-Mediated Autophagy in Neurodegenerative Diseases and Acute Neurological Insults in the Central Nervous System

Kanno

Handa

Murakami

et al. 2022

Cells

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“…Micro-autophagy, a non-selective procedure, is activated commonly to ingest senescent endoplasmic membranes by direct engulfment in the lysosome membrane[ 32 ]; it is the only constitutive autophagy mechanism that triggers small cytoplasmic debris engulfment into the lysosome for degradation[ 31 ]. CMA is a main route for the elimination of cellular aberrant proteins and can provide a cytoprotective effect[ 33 ]; it is an intracellular catabolic pathway that mediates the degradation of soluble cytosolic proteins in lysosomes[ 34 ].…”

Section: Autophagy: the Path And The Mapmentioning

confidence: 99%

Role of autophagy in gastric carcinogenesis

Papaefthymiou

Christodoulidis

Koffas

et al. 2021

WJGO

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Gastric cancer represents a common and highly fatal malignancy, and thus a pathophysiology-based reconsideration is necessary, given the absence of efficient therapeutic regimens. In this regard, emerging data reveal a significant role of autophagy in gastric oncogenesis, progression, metastasis and chemoresistance. Although autophagy comprises a normal primordial process, ensuring cellular homeostasis under energy depletion and stress conditions, alterations at any stage of the complex regulatory system could stimulate a tumorigenic and promoting cascade. Among others, Helicobacter pylori infection induces a variety of signaling molecules modifying autophagy, during acute infection or after chronic autophagy degeneration. Subsequently, defective autophagy allows malignant transformation and upon cancer establishment, an overactive autophagy is stimulated. This overexpressed autophagy provides energy supplies and resistance mechanisms to gastric cancer cells against hosts defenses and anticancer treatment. This review interprets the implicated autophagic pathways in normal cells and in gastric cancer to illuminate the potential preventive, therapeutic and prognostic benefits of understanding and intervening autophagy.

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UBC9‐mediated SUMOylation of Lamin B1 enhances DNA‐damage‐induced nuclear DNA leakage and autophagy after spinal cord injury

Fan,

Lou,

Jin

et al. 2024

Journal Cellular Physiology

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Recent studies have shown that nucleophagy can mitigate DNA damage by selectively degrading nuclear components protruding from the nucleus. However, little is known about the role of nucleophagy in neurons after spinal cord injury (SCI). Western blot analysis and immunofluorescence were performed to evaluate the nucleophagy after nuclear DNA damage and leakage in SCI neurons in vivo and NSC34 expression in primary neurons cultured with oxygen–glucose deprivation (OGD) in vitro, as well as the interaction and colocalization of autophagy protein LC3 with nuclear lamina protein Lamin B1. The effect of UBC9, a Small ubiquitin‐related modifier (SUMO) E2 ligase, on Lamin B1 SUMOylation and nucleophagy was examined by siRNA transfection or 2‐D08 (a small‐molecule inhibitor of UBC9), immunoprecipitation, and immunofluorescence. In SCI and OGD injured NSC34 or primary cultured neurons, neuronal nuclear DNA damage induced the SUMOylation of Lamin B1, which was required by the nuclear Lamina accumulation of UBC9. Furthermore, LC3/Atg8, an autophagy‐related protein, directly bound to SUMOylated Lamin B1, and delivered Lamin B1 to the lysosome. Knockdown or suppression of UBC9 with siRNA or 2‐D08 inhibited SUMOylation of Lamin B1 and subsequent nucleophagy and protected against neuronal death. Upon neuronal DNA damage and leakage after SCI, SUMOylation of Lamin B1 is induced by nuclear Lamina accumulation of UBC9. Furthermore, it promotes LC3‐Lamin B1 interaction to trigger nucleophagy that protects against neuronal DNA damage.

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Chaperone-Mediated Autophagy after Spinal Cord Injury

Cited by 12 publications

References 44 publications

Chaperone-Mediated Autophagy in Neurodegenerative Diseases and Acute Neurological Insults in the Central Nervous System

Chaperone-Mediated Autophagy in Neurodegenerative Diseases and Acute Neurological Insults in the Central Nervous System

Role of autophagy in gastric carcinogenesis

UBC9‐mediated SUMOylation of Lamin B1 enhances DNA‐damage‐induced nuclear DNA leakage and autophagy after spinal cord injury

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