Objectives: Understanding the ischemic injury contribution to Alzheimer’s disease (AD) onset, pinpointing to post-translational modifications, turnover alterations, secretion of proteins and networks identified as AD hallmarks. Materials: Neuronal cultures prepared from hippocampi of E18-E19 embryos from pregnant Sprague Dawley rats. 5%CO2: 95%N2 gaseous mixtures (Sapio); hypoxia chamber (Billups–Rothenberg). Methods: DIV8 neurons were subjected to oxygen and glucose deprivation (OGD). After medium replacement with a glucose-free balanced salt solution (ogR), cells were incubated for 3 hours in the chamber saturated with the gaseous mixture. The restoration solution (glucose and B27) was administrated to neurons (ogR) for one hour (R1h) or overnight (R16h). Results: We observed Tau and amyloid precursor protein (APP) post-translational and protein level modifications after OGD/ogR. Tau cleavage and secretion occurs at R1h through microvesicles (MVs) population, including LC3 and/or LAMP1 positive vesicles, marker of autophagy-mediated secretion (exophagy). In MVs extract we also identified α- and β- C-terminal fragments (CTFs) of APP, and the peptidyl prolyl cis/trans isomerase Pin1. Discussion: MVs represent an intercellular communication delivering multiple cargo with beneficial or harmful messages [1]. Thus, differences in MVs contents after OGD/ogR suggest that ischemia leads to a robust upheaval with the autophagic mechanisms activation resultant in neuron-to-neuron transfer of material with neurodegenerative potential. Conclusions: OGD treatment leads to mis-processed protein unconventional secretion also including exophagy pathway. These proteins represent seeds for protein aggregation according to the “prion-like” propagation mechanism [2] that may represent an early event in AD and proteinopathies.

Lonati, E., Sala, G., Tresoldi, V., Coco, S., Milani, C., Restelli, A., et al. (2016). Ischemic injury elicits the unconventional secretion of protein hallmarks of Alzheimer's disease onset as seeds for interneuronal propagation. In Abstracts for the Second International Meeting of the Milan Center for Neuroscience (Neuromi): Prediction and Prevention of Dementia: New Hope (Milan, July 6-8, 2016) (pp.S34-S35). IOS PRESS.

Ischemic injury elicits the unconventional secretion of protein hallmarks of Alzheimer's disease onset as seeds for interneuronal propagation

LONATI, ELENA RITA
Primo
;
SALA, GESSICA;COCO, SILVIA;MILANI, CHIARA;FARINA, FRANCESCA;BOTTO, LAURA MARIA;SALERNO, DOMENICO;PALESTINI, PAOLA NOVERINA ADA;BULBARELLI, ALESSANDRA
2016

Abstract

Objectives: Understanding the ischemic injury contribution to Alzheimer’s disease (AD) onset, pinpointing to post-translational modifications, turnover alterations, secretion of proteins and networks identified as AD hallmarks. Materials: Neuronal cultures prepared from hippocampi of E18-E19 embryos from pregnant Sprague Dawley rats. 5%CO2: 95%N2 gaseous mixtures (Sapio); hypoxia chamber (Billups–Rothenberg). Methods: DIV8 neurons were subjected to oxygen and glucose deprivation (OGD). After medium replacement with a glucose-free balanced salt solution (ogR), cells were incubated for 3 hours in the chamber saturated with the gaseous mixture. The restoration solution (glucose and B27) was administrated to neurons (ogR) for one hour (R1h) or overnight (R16h). Results: We observed Tau and amyloid precursor protein (APP) post-translational and protein level modifications after OGD/ogR. Tau cleavage and secretion occurs at R1h through microvesicles (MVs) population, including LC3 and/or LAMP1 positive vesicles, marker of autophagy-mediated secretion (exophagy). In MVs extract we also identified α- and β- C-terminal fragments (CTFs) of APP, and the peptidyl prolyl cis/trans isomerase Pin1. Discussion: MVs represent an intercellular communication delivering multiple cargo with beneficial or harmful messages [1]. Thus, differences in MVs contents after OGD/ogR suggest that ischemia leads to a robust upheaval with the autophagic mechanisms activation resultant in neuron-to-neuron transfer of material with neurodegenerative potential. Conclusions: OGD treatment leads to mis-processed protein unconventional secretion also including exophagy pathway. These proteins represent seeds for protein aggregation according to the “prion-like” propagation mechanism [2] that may represent an early event in AD and proteinopathies.
No
abstract + poster
Oxygen and glucose deprivation, Alzheimer's disease, exophagy, microvesicles
English
Second International Meeting of the Milan Center for Neuroscience (Neuromi) Prediction and Prevention of Dementia : New Hope
Lonati, E., Sala, G., Tresoldi, V., Coco, S., Milani, C., Restelli, A., et al. (2016). Ischemic injury elicits the unconventional secretion of protein hallmarks of Alzheimer's disease onset as seeds for interneuronal propagation. In Abstracts for the Second International Meeting of the Milan Center for Neuroscience (Neuromi): Prediction and Prevention of Dementia: New Hope (Milan, July 6-8, 2016) (pp.S34-S35). IOS PRESS.
Lonati, E; Sala, G; Tresoldi, V; Coco, S; Milani, C; Restelli, A; Farina, F; Botto, L; Salerno, D; Palestini, P; Bulbarelli, A
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/128339
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