Targeting Glial Mitochondrial Function for Protection from Cerebral Ischemia: Relevance, Mechanisms, and the Role of MicroRNAs.
Le LiCreed M StaryPublished in: Oxidative medicine and cellular longevity (2016)
Astrocytes and microglia play crucial roles in the response to cerebral ischemia and are effective targets for stroke therapy in animal models. MicroRNAs (miRs) are important posttranscriptional regulators of gene expression that function by inhibiting the translation of select target genes. In astrocytes, miR expression patterns regulate mitochondrial function in response to oxidative stress via targeting of Bcl2 and heat shock protein 70 family members. Mitochondria play an active role in microglial activation, and miRs regulate the microglial neuroinflammatory response. As endogenous miR expression patterns can be altered with exogenous mimics and inhibitors, miR-targeted therapies represent a viable intervention to optimize glial mitochondrial function and improve clinical outcome following cerebral ischemia. In the present article, we review the role that astrocytes and microglia play in neuronal function and fate following ischemic stress, discuss the relevance of mitochondria in the glial response to injury, and present current evidence implicating miRs as critical regulators in the glial mitochondrial response to cerebral ischemia.
Keyphrases
- cerebral ischemia
- neuropathic pain
- long non coding rna
- subarachnoid hemorrhage
- poor prognosis
- cell proliferation
- blood brain barrier
- heat shock protein
- oxidative stress
- brain injury
- spinal cord
- inflammatory response
- gene expression
- spinal cord injury
- long noncoding rna
- transcription factor
- cell death
- dna methylation
- lipopolysaccharide induced
- cancer therapy
- reactive oxygen species
- heat shock
- lps induced
- stem cells
- signaling pathway
- dna damage
- endoplasmic reticulum
- ischemia reperfusion injury
- drug delivery