The spreading of misfolded protein species contributes to the propagation of harmful mediators in proteinopathies, including Alzheimer's disease (AD). Cellular stress circumstances, such as abnormal protein accumulation or nutrient deprivation, elicit the secretion of soluble misprocessed proteins and insoluble aggregates via multiple mechanisms of unconventional secretion. One of them consists in the rerouting of autophagic vacuoles towards exocytosis, an unconventional type of autophagy mediated by caspase-3 activation under starvation. Ischemic injury is a starvation condition characterized by oxygen/nutrient deprivation, whose contribution in AD onset has definitely been endorsed. Thus, we investigated the effect of oxygen-glucose deprivation (OGD), an experimental condition mimicking cerebral ischemia, in search of alteration in Tau processing and secretion in hippocampal neurons primary cultures. Our results showed that OGD caused alterations in Tau phosphorylation and processing, paralleled by an induction of its secretion. Interestingly, together with caspase-3 activation, full-length (FL) and fragmented Tau forms were secreted by their own or through a heterogeneous population of microvesicles (MVs), including autophagosome marker LC3-positive vesicles. Accordingly, confocal microscopy revealed a partial colocalization of intracellular Tau and LC3. Summarizing, our findings indicate that OGD alters Tau intracellular levels and protein processing. Consequently, Tau clearance was stimulated through multiple mechanisms related to unconventional Tau secretion, including exophagy. However, the activation of this response represent a double edge sword, because it could contribute to the spreading of misfolded Tau, a neurodegeneration pathway in AD and other tauopathies.
Pubmed ID: 30421280 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This polyclonal targets SQSTM1/p62
View all literature mentionsThis polyclonal targets Phospho-GSK-3 (Ser9)
View all literature mentionsThis monoclonal targets PARP
View all literature mentionsThis polyclonal targets Beclin-1
View all literature mentionsThis monoclonal targets Tau
View all literature mentionsThis polyclonal targets Actin
View all literature mentionsThis monoclonal targets Flotillin-2
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal targets Rabbit LAMP-1 (CD107a)
View all literature mentionsThis monoclonal targets Mouse GSK3beta Antibodies Clone ZG004
View all literature mentionsThis monoclonal targets Caspase-3 (8G10) Rabbit mAb
View all literature mentionsThis unknown targets Tau
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis unknown targets Tau
View all literature mentionsThis polyclonal targets SQSTM1/p62
View all literature mentionsThis monoclonal targets Flotillin-2
View all literature mentionsThis monoclonal targets Caspase-3 (8G10) Rabbit mAb
View all literature mentionsThis polyclonal targets Rabbit LAMP-1 (CD107a)
View all literature mentionsThis polyclonal targets Phospho-GSK-3 (Ser9)
View all literature mentionsThis monoclonal targets PARP
View all literature mentionsThis polyclonal targets Beclin-1
View all literature mentionsThis monoclonal targets Mouse GSK3beta Antibodies Clone ZG004
View all literature mentionsThis monoclonal targets Tau
View all literature mentionsThis polyclonal targets Actin
View all literature mentions