ER stress and impaired autophagy flux in neuronal degeneration and brain injury.
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.
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.
Yan
Y
Yin
Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213, United States.
George
G
Sun
Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213, United States.
Eric
E
Li
Department of Biological Science, University of Pittsburgh, Pittsburgh, PA 15213, United States.
Kirill
K
Kiselyov
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.
Dandan
D
Sun
D000368:Aged; D000375:Aging / Q000502:physiology*; D001343:Autophagy / Q000187:drug effects / Q000502:physiology; D001930:Brain Injuries / Q000188:drug therapy / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000502:physiology; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology
D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D004281:Docosahexaenoic Acids
Autophagy; Brain aging; Docosahexaenoic acid; Lysosome; Stroke; Traumatic brain injury