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Ageing Res Rev. 2017 Mar;34:3-14. doi: 10.1016/j.arr.2016.08.008. Epub 2016 Sep 1.

ER stress and impaired autophagy flux in neuronal degeneration and brain injury.

Author information

1
Department of Neurology, The Second Hospital of Dalian Medical University, Dalian 116023, PR China; Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213, United States. Electronic address: yanyin1208@126.com.
2
Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213, United States.
3
Department of Biological Science, University of Pittsburgh, Pittsburgh, PA 15213, United States.
4
Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213, United States; Veterans Affairs Pittsburgh Health Care System, Geriatric Research, Education and Clinical Center, Pittsburgh, PA 15213, United States. Electronic address: sund@upmc.edu.

Abstract

Autophagy is a highly controlled lysosome-mediated function in eukaryotic cells to eliminate damaged or aged long-lived proteins and organelles. It is required for restoring cellular homeostasis in cell survival under multiple stresses. Autophagy is known to be a double-edged sword because too much activation or inhibition of autophagy can disrupt homeostatic degradation of protein and organelles within the brain and play a role in neuronal cell death. Many factors affect autophagy flux function in the brain, including endoplasmic reticulum (ER) stress, oxidative stress, and aging. Newly emerged research indicates that altered autophagy flux functionality is involved in neurodegeneration of the aged brain, chronic neurological diseases, and after traumatic and ischemic brain injuries. In search to identify neuroprotective agents that may reduce oxidative stress and stimulate autophagy, one particular neuroprotective agent docosahexaenoic acid (DHA) presents unique functions in reducing ER and oxidative stress and modulating autophagy. This review will summarize the recent findings on changes of autophagy in aging, neurodegenerative diseases, and brain injury after trauma or ischemic strokes. Discussion of DHA functions is focused on modulating ER stress and autophagy in regard to its neuroprotection and anti-tumor functions.

KEYWORDS:

Autophagy; Brain aging; Docosahexaenoic acid; Lysosome; Stroke; Traumatic brain injury

PMID:
27594375
PMCID:
PMC5250579
DOI:
10.1016/j.arr.2016.08.008
[Indexed for MEDLINE]
Free PMC Article

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