The cytoplasmic nuclear shuttling of Beclin 1 in neurons with Alzheimer's disease-like injury.
Neurosci Lett
; 661: 63-70, 2017 Nov 20.
Article
de En
| MEDLINE
| ID: mdl-28964771
ABSTRACT
The abnormal expression of the autophagy-related protein Beclin 1 has been implicated in Alzheimer's disease (AD) brains, whereas the precise involvement of Caspase-mediated Beclin 1 cleavage in AD neurons has not yet been fully clarified. In this study, we investigated the distribution of Beclin 1 fragments in neurons with AD-like injury. Our results demonstrated that Beclin 1 was expressed in neurons but not in astrocytes in both neuron-glia co-cultures and in cortical tissue slices. The full length and C-terminal fragments of human Beclin 1 was mainly expressed in cytoplasm, while the N-terminal fragment of Beclin 1 was predominantly localized in nucleus. Compared to amyloid-ß (Aß)42-1 treatment control, exposure of PC12 cells or cortical neurons to Aß1-42 resulted in cell injury, with the appearance of neuritic shortening, reduced nuclear diameter in PC12 cells, beading formation and fragmentation in cortical neurons. A partial nuclear translocation of Beclin 1 was detected in cells incubated with Aß1-42, which could be inhibited by the administration of pan-Caspase inhibitor or Caspase 3 specific inhibitor. Moreover, Beclin 1 mutation at 146/149 sites was resistant to Aß1-42-induced nuclear translocation. The nuclear translocation of Beclin 1 could also been detected in the brains of 12-month-old APPSwe/PS1dE9 transgenic mice. Our findings suggest that after Caspase 3-mediated Beclin 1 cleavage at 146/149 sites, the N-terminal fragments of Beclin 1 may partially translocate into nuclei in neurons subjected to AD-like injury.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Lésions encéphaliques
/
Caspase-3
/
Maladie d'Alzheimer
/
Bécline-1
/
Neurones
Limites:
Animals
/
Female
/
Humans
/
Male
Langue:
En
Journal:
Neurosci Lett
Année:
2017
Type de document:
Article
Pays d'affiliation:
Chine