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Attenuation of Ischemic Stroke-Caused Brain Injury by a Monoamine Oxidase Inhibitor Involves Improved Proteostasis and Reduced Neuroinflammation

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Abstract

Mitochondrial dysfunction and oxidative stress play a key role in ischemia/reperfusion (I/R) induced brain injury. We previously showed that ubiquilin-1 (Ubqln1), a ubiquitin-like protein, improves proteostasis and protects brains against oxidative stress and I/R induced brain injury. We demonstrate here that nialamide (NM), a non-selective monoamine oxidase (MAO) inhibitor, upregulated Ublqn1 and protected neurons from oxygen-glucose deprivation- and I/R-caused cell death in in vitro and in vivo, respectively. Post-ischemic administration of the NM in a stroke mouse model even at 3 h following I/R still reduced neuronal injury and improved functional recovery and survival. Treating stroke animals with NM also increased the association of Ubqln1 with mitochondria and decreased the total oxidized and polyubiquitinated protein levels. Intriguingly, NM-enhanced proteostasis was also associated with reduced I/R-caused neuroinflammation, as reflected by attenuated activation of microglia and astrocytes as well as reduced TNF-α level. Thus, our results suggest that MAO inhibition-induced neuroprotection following I/R involves improved proteostasis and reduced neuroinflammation.

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Funding

This study was funded by the National Institute of Neurological Disorders and Stroke under research grant NS088084.

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Authors and Affiliations

  1. Division of Basic Biomedical Sciences and Center for Brain and Behavior Research, Sanford School of Medicine, University of South Dakota, Vermillion, SD, 57069, USA

    Yanying Liu, Shelley Feng, Kalpana Subedi & Hongmin Wang

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  1. Yanying Liu
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  2. Shelley Feng
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Correspondence to Hongmin Wang.

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Liu, Y., Feng, S., Subedi, K. et al. Attenuation of Ischemic Stroke-Caused Brain Injury by a Monoamine Oxidase Inhibitor Involves Improved Proteostasis and Reduced Neuroinflammation. Mol Neurobiol 57, 937–948 (2020). https://doi.org/10.1007/s12035-019-01788-2

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