Objectives. To understand brain ischemia injury contribution to Alzheimer’s disease (AD) onset, looking for post-translational modifications, turnover alterations and AD hallmarks secretion such as tau and amyloid precursor protein (APP), associated to autophagy activation. Methods. Rat cultured hippocampal neurons are subjected to oxygen glucose deprivation (OGD) followed by normal culture condition restoration (R), mimicking an ischemia/reperfusion (I/R) event. Afterwards AD hallmarks and autophagy markers expression and secretion are analyzed in the cells lysate and in microvescicles (MVs) isolated from culture medium. Confocal microscopy is employed to evaluate the potential re- and co-localization of tau and autophagic markers after treatment. Results. In our cellular model subjected to OGD/R, we observed tau and APP post-translational and protein level modifications in parallel to the autophagic markers (LC3II and beclin-1) expression alterations. Moreover, OGD/R treatment elicits a time-dependent increase in tau and APP C-terminal fragments (CTF) secretion by means of a heterogeneous MV population, including a group of LC3II positive vescicles. Preliminary data obtained by confocal microscopy suggest that LC3 might undergo re-localization after OGD/R treatment. Conclusions. The obtained results suggest that OGD treatment leads to multiple unconventional secretion mechanisms for tau and APP CTFs, in which autophagy activation seems to partially outcome in the exophagy secretory pathway. Although exophagy might be a defensive mechanism to prevent intracellular accumulation of misfolded proteins under conventional autophagy alteration, the secretion of misprocessed proteins has been recently associated to dendritic degeneration and neuronal death becoming a possible link to Alzheimer’s disease.

Lonati, E., Sala, G., Tresoldi, V., Coco, S., Masserini, M., Palestini, P., et al. (2015). AUTOPHAGY ALTERATION UNDER ISCHEMIC CONDITION: A POSSIBLE LINK TO ALZHEIMER'S DISEASE. In Mechanisms, Clinical Strategies, and Promising Treatments of Neurodegenerative Diseases. 12th International Conference AD/PDTM Nice, France, March 18-22, 2015: Abstracts (pp.482-482).

AUTOPHAGY ALTERATION UNDER ISCHEMIC CONDITION: A POSSIBLE LINK TO ALZHEIMER'S DISEASE

LONATI, ELENA RITA
Primo
;
SALA, GESSICA
Secondo
;
COCO, SILVIA;MASSERINI, MASSIMO ERNESTO;PALESTINI, PAOLA NOVERINA ADA
Penultimo
;
BULBARELLI, ALESSANDRA
Ultimo
2015

Abstract

Objectives. To understand brain ischemia injury contribution to Alzheimer’s disease (AD) onset, looking for post-translational modifications, turnover alterations and AD hallmarks secretion such as tau and amyloid precursor protein (APP), associated to autophagy activation. Methods. Rat cultured hippocampal neurons are subjected to oxygen glucose deprivation (OGD) followed by normal culture condition restoration (R), mimicking an ischemia/reperfusion (I/R) event. Afterwards AD hallmarks and autophagy markers expression and secretion are analyzed in the cells lysate and in microvescicles (MVs) isolated from culture medium. Confocal microscopy is employed to evaluate the potential re- and co-localization of tau and autophagic markers after treatment. Results. In our cellular model subjected to OGD/R, we observed tau and APP post-translational and protein level modifications in parallel to the autophagic markers (LC3II and beclin-1) expression alterations. Moreover, OGD/R treatment elicits a time-dependent increase in tau and APP C-terminal fragments (CTF) secretion by means of a heterogeneous MV population, including a group of LC3II positive vescicles. Preliminary data obtained by confocal microscopy suggest that LC3 might undergo re-localization after OGD/R treatment. Conclusions. The obtained results suggest that OGD treatment leads to multiple unconventional secretion mechanisms for tau and APP CTFs, in which autophagy activation seems to partially outcome in the exophagy secretory pathway. Although exophagy might be a defensive mechanism to prevent intracellular accumulation of misfolded proteins under conventional autophagy alteration, the secretion of misprocessed proteins has been recently associated to dendritic degeneration and neuronal death becoming a possible link to Alzheimer’s disease.
No
abstract + poster
Scientifica
Alzheimer's disease, Ischemia, Tau protein, autophagy
English
AD/PD 2015
978-3-318-05023-3
Lonati, E., Sala, G., Tresoldi, V., Coco, S., Masserini, M., Palestini, P., et al. (2015). AUTOPHAGY ALTERATION UNDER ISCHEMIC CONDITION: A POSSIBLE LINK TO ALZHEIMER'S DISEASE. In Mechanisms, Clinical Strategies, and Promising Treatments of Neurodegenerative Diseases. 12th International Conference AD/PDTM Nice, France, March 18-22, 2015: Abstracts (pp.482-482).
Lonati, E; Sala, G; Tresoldi, V; Coco, S; Masserini, M; Palestini, P; Bulbarelli, A
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/80300
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