The Role of Mitochondrial and Endoplasmic Reticulum Reactive Oxygen Species Production in Models of Perinatal Brain Injury

• Recent Advances and Critical Issues: Mechanisms underlying ER stress-associated ROS production have been primarily elucidated using either non-neuronal cells or adult neurodegenerative experimental models. Findings from mature brain cannot be simply transferred to the immature brain. Therefore, age-specific studies investigating ER stress modulators may help investigate ER stress-associated ROS pathways in the immature brain. New therapeutics such as mitochondrial site-specific ROS inhibitors that selectively inhibit superoxide (O-2(center dot-))/hydrogen peroxide (H2O2) production are currently being developed. Future Directions: Because ER stress and oxidative stress accentuate each other, a combinatorial therapy utilizing both antioxidants and ER stress inhibitors may prove to be more protective against perinatal brain injury. Moreover, multiple relevant targets need to be identified for targeting ROS before they are formed. The role of organelle-specific ROS in brain repair needs investigation.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Nyckelord

reactive oxygen species

neonatal hypoxia-ischemia

mitochondria

endoplasmic reticulum

sirtuins

antioxidants

manganese superoxide-dismutase

nrf2-inducible antioxidant defense

hypoxic-ischemic injury

oxidative stress

nadph oxidase

hydrogen-peroxide

free-radicals

er stress

sirt3 deacetylates

electron-transport

Biochemistry & Molecular Biology

Endocrinology & Metabolism

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