コンテンツへスキップ
Merck
  • The lipid phosphatase Synaptojanin 1 undergoes a significant alteration in expression and solubility and is associated with brain lesions in Alzheimer's disease.

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

Acta neuropathologica communications (2020-06-05)
Kunie Ando, Marième Ndjim, Sabrina Turbant, Gaëlle Fontaine, Gustavo Pregoni, Luce Dauphinot, Zehra Yilmaz, Valérie Suain, Salwa Mansour, Michèle Authelet, Robert De Dekker, Karelle Leroy, Benoît Delatour, Charles Duyckaerts, Marie-Claude Potier, Jean-Pierre Brion
要旨

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 post-mortem 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.

材料
製品番号
ブランド
製品内容

Sigma-Aldrich
モノクローナル抗FLAG® M2抗体 マウス宿主抗体, clone M2, purified immunoglobulin (Purified IgG1 subclass), buffered aqueous solution (10 mM sodium phosphate, 150 mM NaCl, pH 7.4, containing 0.02% sodium azide)
Sigma-Aldrich
ホスファターゼインヒビターカクテル2, aqueous solution (dark coloration may develop upon storage, which does not affect the activity)
Sigma-Aldrich
モノクロナール抗β-アクチン マウス宿主抗体, clone AC-15, ascites fluid
Sigma-Aldrich
N-ラウロイルサルコシン ナトリウム塩, ≥94%
Sigma-Aldrich
カルパインインヒビター I, ≥97% (TLC), powder
Sigma-Aldrich
抗マウスIgG (全分子)-ペルオキシダーゼ ヒツジ宿主抗体, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
抗SYNJ1抗体 ウサギ宿主抗体, affinity isolated antibody, buffered aqueous glycerol solution