The lipid phosphatase synaptojanin 1 ...
Document type :
Article dans une revue scientifique: Article original
PMID :
Permalink :
Title :
The lipid phosphatase synaptojanin 1 undergoes a significant alteration in expression and solubility and is associated with brain lesions in alzheimer''s disease
Author(s) :
Ando, Kunie [Auteur]
Ndjim, Marieme [Auteur]
Turbant, Sabrina [Auteur]
Fontaine, Gaëlle [Auteur]
Pregoni, Gustavo [Auteur]
Dauphinot, Luce [Auteur]
Yilmaz, Zehra [Auteur]
Suain, Valerie [Auteur]
Mansour, Salwa [Auteur]
Authelet, Michele [Auteur]
De Dekker, Robert [Auteur]
Leroy, Karelle [Auteur]
Delatour, Benoit [Auteur]
Duyckaerts, Charles [Auteur]
Potier, Marie-Claude [Auteur]
Brion, Jean-Pierre [Auteur]
Ndjim, Marieme [Auteur]
Turbant, Sabrina [Auteur]
Fontaine, Gaëlle [Auteur]
Pregoni, Gustavo [Auteur]
Dauphinot, Luce [Auteur]
Yilmaz, Zehra [Auteur]
Suain, Valerie [Auteur]
Mansour, Salwa [Auteur]
Authelet, Michele [Auteur]
De Dekker, Robert [Auteur]
Leroy, Karelle [Auteur]
Delatour, Benoit [Auteur]
Duyckaerts, Charles [Auteur]
Potier, Marie-Claude [Auteur]
Brion, Jean-Pierre [Auteur]
Journal title :
Acta neuropathologica communications
Abbreviated title :
Acta Neuropathol Commun
Volume number :
8
Pages :
79
Publication date :
2020-06-03
ISSN :
2051-5960
Keyword(s) :
Tau
Alzheimer''s disease
SYNJ1
Amyloid beta
Neurofibrillary tangles
Hirano bodies
Phosphatidylinositol
Alzheimer''s disease
SYNJ1
Amyloid beta
Neurofibrillary tangles
Hirano bodies
Phosphatidylinositol
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
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 ...
Show more >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.Show less >
Show more >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.Show less >
Language :
Anglais
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
CHU Lille
Inserm
Université de Lille
Inserm
Université de Lille
Collections :
Research team(s) :
Alzheimer et Tauopathies
Développement et plasticité du cerveau neuro-endocrine
Développement et plasticité du cerveau neuro-endocrine
Submission date :
2021-06-23T13:46:31Z
2021-07-12T09:10:07Z
2021-07-12T09:10:07Z