Autophagy and protein aggregation after brain ischemia
Open Access
- 15 September 2010
- journal article
- Published by Wiley in Journal of Neurochemistry
- Vol. 115 (1), 68-78
- https://doi.org/10.1111/j.1471-4159.2010.06905.x
Abstract
J. Neurochem. (2010) 115, 68–78. Abstract Autophagy is the main degradation pathway responsible for eliminating abnormal protein aggregates and damaged organelles prevalent in neurons after transient cerebral ischemia. This study investigated whether accumulation of protein aggregate‐associated organelles in post‐ischemic neurons is a consequence of changes in autophagy. Electron microscopic analysis indicated that both autophagosomes and autolysosomes are significantly up‐regulated in hippocampal CA1 and DG neurons after ischemia. The microtubule‐associated protein light chain 3 (LC3)‐II conjugate, a marker for autophagosomes assessed by western blotting, was up‐regulated in post‐ischemic brain tissues. Confocal microscopy showed that LC3 isoforms were located in living post‐ischemic neurons. Treatment with chloriquine resulted in accumulation of LC3‐II in sham‐operated rats, but did not further change the LC3‐II levels in post‐ischemic brain tissues. The results indicate that at least part of the accumulation of protein aggregate‐associated organelles seen following ischemia is likely to be because of failure of the autophagy pathway. The resulting protein aggregation on subcellular organelle membranes could lead to multiple organelle damage and to delayed neuronal death after transient cerebral ischemia.Keywords
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