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Crosstalk Between Endoplasmic Reticulum Stress, Oxidative Stress, and Autophagy: Potential Therapeutic Targets for Acute CNS Injuries

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Abstract

Endoplasmic reticulum (ER) stress induces a variety of neuronal cell death pathways that play a critical role in the pathophysiology of stroke. ER stress occurs when unfolded/misfolded proteins accumulate and the folding capacity of ER chaperones exceeds the capacity of ER lumen to facilitate their disposal. As a consequence, a complex set of signaling pathways will be induced that transmit from ER to cytosol and nucleus to compensate damage and to restore the normal cellular homeostasis, collectively known as unfolded protein response (UPR). However, failure of UPR due to severe or prolonged stress leads to cell death. Following acute CNS injuries, chronic disturbances in protein folding and oxidative stress prolong ER stress leading to sustained ER dysfunction and neuronal cell death. While ER stress responses have been well studied after stroke, there is an emerging need to study the association of ER stress with other cell pathways that exacerbate neuronal death after an injury. In this review, we summarize the current understanding of the role for ER stress in acute brain injuries, highlighting the diverse molecular mechanisms associated with ER stress and its relation to oxidative stress and autophagy. We also discussed the existing and developing therapeutic options aimed to reduce ER stress to protect the CNS after acute injuries.

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Authors and Affiliations

  1. Department of Neurological Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, WI, 53792, USA

    Venkata Prasuja Nakka & Raghu Vemuganti

  2. Department of Biotechnology & Bioinformatics, School of Life sciences, University of Hyderabad, Hyderabad, India

    Venkata Prasuja Nakka & Phanithi Prakash-babu

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  1. Venkata Prasuja Nakka
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Nakka, V.P., Prakash-babu, P. & Vemuganti, R. Crosstalk Between Endoplasmic Reticulum Stress, Oxidative Stress, and Autophagy: Potential Therapeutic Targets for Acute CNS Injuries. Mol Neurobiol 53, 532–544 (2016). https://doi.org/10.1007/s12035-014-9029-6

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