LC3, an autophagosome marker, is expressed on oligodendrocytes in Nasu-Hakola disease brains

Satoh, Jun‐ichi; Motohashi, Nobutaka; Kino, Yoshihiro; Ishida, Tsuyoshi; Yagishita, Saburo; Jinnai, Kenji; Arai, Nobutaka; Nakamagoe, Kiyotaka; Tamaoka, Akira; Saito, Yuko; Arima, Kunimasa

doi:10.1186/1750-1172-9-68

Cited by 29 publications

(28 citation statements)

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“…SIRT1 deacetylated LC3, which promoted autophagic activities as the main marker of autophagosome (Figure 11) [45]. Picroside II controlled the autophagic activity of pancreatic cells by affecting the expression of NF- κ B.…”

Section: Discussionmentioning

confidence: 99%

Picroside II Shows Protective Functions for Severe Acute Pancreatitis in Rats by Preventing NF‐κB‐Dependent Autophagy

Piao¹,

Liu

Guo

et al. 2017

Oxidative Medicine and Cellular Longevity

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Picroside II, from the herb Picrorhiza scrophulariiflora Pennell, has antioxidant and anti-inflammatory activities. However, its function on severe acute pancreatitis (SAP) and molecular mechanism remains unknown. The effects of picroside II on the SAP induced by cerulean were investigated. SAP rats were treated with picroside II (25 mg/kg). The severity of SAP was evaluated by using biochemical and histological analyses. Pancreatic cancer cell PANC-1 was transfected with ptfLC3 (an indicator of autophagic activity), pcDNA3.1-NF-κB (nuclear factor kappa B), and pTZU6+1-NF-κB-shRNA and then treated with picroside II. Relative molecules related with NF-κB-dependent autophagy were detected by using Western blot. Autophagic activities were observed by phase-contrast and fluorescent microscopes. Acetylated LC3 was detected by immunoprecipitation. The results showed that picroside II treatment reduced the level of ALT, AST, NF-κB, IL-1β, IL-6, TNF-α, and SIRT1 (NAD+-dependent deacetylase) and increased the level of SOD and GSH. The autophagic activity was reduced when NF-κB was silenced, and the levels of TNF-α and SIRT1 were reduced. In contrast, the overexpression of NF-κB increased autophagic activity and the level of TNF-α, which activated SIRT1. SIRT1 deacetylated LC3 and increased autophagic activities. Picroside II ameliorates SAP by improving antioxidant and anti-inflammtory activities of SAP models via NF-κB-dependent autophagy.

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Section: Discussionmentioning

confidence: 99%

Picroside II Shows Protective Functions for Severe Acute Pancreatitis in Rats by Preventing NF‐κB‐Dependent Autophagy

Piao¹,

Liu

Guo

et al. 2017

Oxidative Medicine and Cellular Longevity

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“…We examined 10 autopsied brains of ALSP patients from six families (six males and four females; ages at autopsy: 41–63 years; mean age ± standard deviation, 53.1 ± 7.7 years) and eight autopsied brains of N‐HD patients from seven families (four males and four females; ages at autopsy: 38–55 years, 43.9 ± 5.9 years) . All of these patients were Japanese.…”

Section: Methodsmentioning

confidence: 99%

Adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and Nasu–Hakola disease: lesion staging and dynamic changes of axons and microglial subsets

et al. 2017

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The brains of 10 Japanese patients with adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) encompassing hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) and pigmentary orthochromatic leukodystrophy (POLD) and eight Japanese patients with Nasu-Hakola disease (N-HD) and five age-matched Japanese controls were examined neuropathologically with special reference to lesion staging and dynamic changes of microglial subsets. In both diseases, the pathognomonic neuropathological features included spherically swollen axons (spheroids and globules), axon loss and changes of microglia in the white matter. In ALSP, four lesion stages based on the degree of axon loss were discernible: Stage I, patchy axon loss in the cerebral white matter without atrophy; Stage II, large patchy areas of axon loss with slight atrophy of the cerebral white matter and slight dilatation of the lateral ventricles; Stage III, extensive axon loss in the cerebral white matter and dilatation of the lateral and third ventricles without remarkable axon loss in the brainstem and cerebellum; Stage IV, devastated cerebral white matter with marked dilatation of the ventricles and axon loss in the brainstem and/or cerebellum. Internal capsule and pontine base were relatively well preserved in the N-HD, even at Stage IV, and the swollen axons were larger with a higher density in the ALSP. Microglial cells immunopositive for CD68, CD163 or CD204 were far more obvious in ALSP, than in N-HD, and the shape and density of the cells changed in each stage. With progression of the stage, clinical symptoms became worse to apathetic state, and epilepsy was frequently observed in patients at Stages III and IV in both diseases. From these findings, it is concluded that (i) shape, density and subsets of microglia change dynamically along the passage of stages and (ii) increase of IBA-1-, CD68-, CD163- and CD204-immunopositive cells precedes loss of axons in ALSP.

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“…Perhaps, the loss of myelin in PLOSL results from dysfunctional oligodendrocytes autophagy induced by abnormal TREM2- or DAP12-deficient microglia. 74 Alternatively, loss of TREM2-DAP12 signaling in oligodendrocytes themselves could contribute to oligodendrocyte apoptosis or a defect in oligodendrocyte function leading to loss of myelin maintenance. 74 In support of this hypothesis, DAP12-deficient mice and DAP12-loss-of- function (Kδ75) transgenic mice expressing mutation of tyrosine 75 (Y75) within the DAP12 ITAM have decreased myelin.…”

Section: Trem2-dap12 Dysfunction In Ploslmentioning

confidence: 99%

The TREM2-DAP12 signaling pathway in Nasu–Hakola disease: a molecular genetics perspective

Xing¹,

Titus²,

Humphrey³

2015

RRBC

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Nasu–Hakola disease or polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) is a rare recessively inherited disease that is associated with early dementia and bone cysts with fractures. Here, we review the genetic causes of PLOSL with loss-of-function mutations or deletions in one of two genes, TYROBP and TREM2, encoding for two proteins DNAX-activating protein 12 (DAP12) and triggering receptor expressed on myeloid cells-2 (TREM2). TREM2 and DAP12 form an immunoreceptor signaling complex that mediates myeloid cell, including microglia and osteoclasts, development, activation, and function. Functionally, TREM2-DAP12 mediates osteoclast multi-nucleation, migration, and resorption. In microglia, TREM2-DAP12 participates in recognition and apoptosis of neuronal debris and amyloid deposits. Review of the complex immunoregulatory roles of TREM2-DAP12 in the innate immune system, where it can both promote and inhibit pro-inflammatory responses, is given. Little is known about the function of TREM2-DAP12 in normal brain homeostasis or in pathological central nervous system diseases. Based on the state of the field, genetic testing now aids in diagnosis of PLOSL, but therapeutics and interventions are still under development.

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LC3, an autophagosome marker, is expressed on oligodendrocytes in Nasu-Hakola disease brains

Cited by 29 publications

References 50 publications

Picroside II Shows Protective Functions for Severe Acute Pancreatitis in Rats by Preventing NF‐κB‐Dependent Autophagy

Picroside II Shows Protective Functions for Severe Acute Pancreatitis in Rats by Preventing NF‐κB‐Dependent Autophagy

Adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and Nasu–Hakola disease: lesion staging and dynamic changes of axons and microglial subsets

The TREM2-DAP12 signaling pathway in Nasu–Hakola disease: a molecular genetics perspective

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LC3, an autophagosome marker, is expressed on oligodendrocytes in Nasu-Hakola disease brains

Cited by 29 publications

References 50 publications

Picroside II Shows Protective Functions for Severe Acute Pancreatitis in Rats by Preventing NF‐κB‐Dependent Autophagy

Picroside II Shows Protective Functions for Severe Acute Pancreatitis in Rats by Preventing NF‐κB‐Dependent Autophagy

Adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and Nasu–Hakola disease: lesion staging and dynamic changes of axons and microglial subsets

The TREM2-DAP12 signaling pathway in Nasu&ndash;Hakola disease: a molecular genetics perspective

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The TREM2-DAP12 signaling pathway in Nasu–Hakola disease: a molecular genetics perspective