Picalm reduction exacerbates tau pathology in a murine tauopathy model

Ando, Kunie; Decker, Robert De; Vergara, Cristina; Yilmaz, Zehra; Mansour, Salwa; Suain, Valérie; Sleegers, Kristel; Fisenne, Marie-Ange De; Houben, Sarah; Potier, Marie‐Claude; Duyckaerts, Charles; Watanabe, Toshio; Buée, Luc; Leroy, Karelle; Brion, Jean Pierre

doi:10.1007/s00401-020-02125-x

Cited by 28 publications

(34 citation statements)

References 67 publications

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“…All these antibodies were diluted in the washing buffer supplemented with 5% of bovine serum and 0.02% azide. The rabbit polyclonal antibody B19 that recognizes all isoforms of tau 83,84 (kindly provided by Jean-Pierre Brion, Université libre de Bruxelles) was diluted at 1/2,000 in PBS supplemented with 2% BSA and 0.08% azide. Diluted antibodies were incubated with the membranes overnight under agitation at 4 °C.…”

Section: Western Blot 20 μG Of Protein Lysates or Samples Collected mentioning

confidence: 99%

Efficiency of the four proteasome subtypes to degrade ubiquitinated or oxidized proteins

Habib

Plaen

Stroobant

et al. 2020

Sci Rep

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The proteasome is responsible for selective degradation of proteins. It exists in mammalian cells under four main subtypes, which differ by the combination of their catalytic subunits: the standard proteasome (β1–β2–β5), the immunoproteasome (β1i–β2i–β5i) and the two intermediate proteasomes (β1–β2–β5i and β1i–β2–β5i). The efficiency of the four proteasome subtypes to degrade ubiquitinated or oxidized proteins remains unclear. Using cells expressing exclusively one proteasome subtype, we observed that ubiquitinated p21 and c-myc were degraded at similar rates, indicating that the four 26S proteasomes degrade ubiquitinated proteins equally well. Under oxidative stress, we observed a partial dissociation of 26S into 20S proteasomes, which can degrade non-ubiquitinated oxidized proteins. Oxidized calmodulin and hemoglobin were best degraded in vitro by the three β5i-containing 20S proteasomes, while their native forms were not degraded. Circular dichroism analyses indicated that ubiquitin-independent recognition of oxidized proteins by 20S proteasomes was triggered by the disruption of their structure. Accordingly, β5i-containing 20S proteasomes degraded unoxidized naturally disordered protein tau, while 26S proteasomes did not. Our results suggest that the three β5i-containing 20S proteasomes, namely the immunoproteasome and the two intermediate proteasomes, might help cells to eliminate proteins containing disordered domains, including those induced by oxidative stress.

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Section: Western Blot 20 μG Of Protein Lysates or Samples Collected mentioning

confidence: 99%

Efficiency of the four proteasome subtypes to degrade ubiquitinated or oxidized proteins

Habib

Plaen

Stroobant

et al. 2020

Sci Rep

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“…Recent studies have shown that the phosphatidylinositol-binding clathrin assembly protein (PICALM) is involved in tau autophagy and clearance [ 96 , 97 ]. PICALM has also been found to be involved in autophagy in vivo and in vitro, including elongation of phagocytes, formation of autophagosomes, and fusion between autophagosomes with lysosomes [ 98 , 99 ].…”

Section: Autophagy and Nddsmentioning

confidence: 99%

Melatonin and Autophagy in Aging-Related Neurodegenerative Diseases

Luo

Sandhu

Rungratanawanich

et al. 2020

IJMS

104

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With aging, the nervous system gradually undergoes degeneration. Increased oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, and cell death are considered to be common pathophysiological mechanisms of various neurodegenerative diseases (NDDs) such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), organophosphate-induced delayed neuropathy (OPIDN), and amyotrophic lateral sclerosis (ALS). Autophagy is a cellular basic metabolic process that degrades the aggregated or misfolded proteins and abnormal organelles in cells. The abnormal regulation of neuronal autophagy is accompanied by the accumulation and deposition of irregular proteins, leading to changes in neuron homeostasis and neurodegeneration. Autophagy exhibits both a protective mechanism and a damage pathway related to programmed cell death. Because of its “double-edged sword”, autophagy plays an important role in neurological damage and NDDs including AD, PD, HD, OPIDN, and ALS. Melatonin is a neuroendocrine hormone mainly synthesized in the pineal gland and exhibits a wide range of biological functions, such as sleep control, regulating circadian rhythm, immune enhancement, metabolism regulation, antioxidant, anti-aging, and anti-tumor effects. It can prevent cell death, reduce inflammation, block calcium channels, etc. In this review, we briefly discuss the neuroprotective role of melatonin against various NDDs via regulating autophagy, which could be a new field for future translational research and clinical studies to discover preventive or therapeutic agents for many NDDs.

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“…The sarkosyl-soluble supernatant was removed, and sarkosylinsoluble pellets were rinsed briefly with 500 μl of 50 mM Tris-HCl (pH 7.4) and re-suspended in 200 μl of 50 mM Tris-HCl (pH 7.4) by vigorous pipetting. Sarkosylinsoluble fractions were analysed by western blotting (WB) and transmission electron microscopy as previously described [3,4].…”

Section: Preparation Of Brain Homogenates For Biochemical Analysismentioning

confidence: 99%

The lipid phosphatase Synaptojanin 1 undergoes a significant alteration in expression and solubility and is associated with brain lesions in Alzheimer’s disease

Ando

Ndjim

Turbant

et al. 2020

acta neuropathol commun

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Synaptojanin 1 (SYNJ1) is a brain-enriched lipid phosphatase critically involved in autophagosomal/endosomal trafficking, synaptic vesicle recycling and metabolism of phosphoinositides. Previous studies suggest that SYNJ1 polymorphisms have significant impact on the age of onset of Alzheimer's disease (AD) and that SYNJ1 is involved in amyloid-induced toxicity. Yet SYNJ1 protein level and cellular localization in post-mortem human AD brain tissues have remained elusive. This study aimed to examine whether SYNJ1 localization and expression are altered in postmortem AD brains. We found that SYNJ1 is accumulated in Hirano bodies, plaque-associated dystrophic neurites and some neurofibrillary tangles (NFTs). SYNJ1 immunoreactivity was higher in neurons and in the senile plaques in AD patients carrying one or two ApolipoproteinE (APOE) ε4 allele(s). In two large cohorts of APOE-genotyped controls and AD patients, SYNJ1 transcripts were significantly increased in AD temporal isocortex compared to control. There was a significant increase in SYNJ1 transcript in APOEε4 carriers compared to non-carriers in AD cohort. SYNJ1 was systematically co-enriched with PHF-tau in the sarkosyl-insoluble fraction of AD brain. In the RIPA-insoluble fraction containing protein aggregates, SYNJ1 proteins were significantly increased and observed as a smear containing full-length and cleaved fragments in AD brains. In vitro cleavage assay showed that SYNJ1 is a substrate of calpain, which is highly activated in AD brains. Our study provides evidence of alterations in SYNJ1 mRNA level and SYNJ1 protein degradation, solubility and localization in AD brains.

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Picalm reduction exacerbates tau pathology in a murine tauopathy model

Cited by 28 publications

References 67 publications

Efficiency of the four proteasome subtypes to degrade ubiquitinated or oxidized proteins

Efficiency of the four proteasome subtypes to degrade ubiquitinated or oxidized proteins

Melatonin and Autophagy in Aging-Related Neurodegenerative Diseases

The lipid phosphatase Synaptojanin 1 undergoes a significant alteration in expression and solubility and is associated with brain lesions in Alzheimer’s disease

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