MicroRNAs as Effectors of Brain Function with Roles in Ischemia and Injury, Neuroprotection, and Neurodegeneration

Abstract

MicroRNAs are small RNAs that function as regulators of posttranscriptional gene expression. MicroRNAs are encoded by genes, and processed to form ribonucleoprotein complexes that bind to messenger RNA (mRNA) targets to repress translation or degrade mRNA transcripts. The microRNAs are particularly abundant in the brain where they serve as effectors of neuronal development and maintenance of the neuronal phenotype. They are also expressed in dendrites where they regulate spine structure and function as effectors in synaptic plasticity. MicroRNAs have been evaluated for their roles in brain ischemia, traumatic brain injury, and spinal cord injury, and in functional recovery after ischemia. They also serve as mediators in the brain’s response to ischemic preconditioning that leads to endogenous neuroprotection. In addition, microRNAs are implicated in neurodegenerative disorders, including Alzheimer’s, Huntington, Parkinson, and Prion disease. The discovery of microRNAs has expanded the potential for human diseases to arise from genetic mutations in microRNA genes or sequences within their target mRNAs. This review discusses microRNA discovery, biogenesis, mechanisms of gene regulation, their expression and function in the brain, and their roles in brain ischemia and injury, neuroprotection, and neurodegeneration.

Epigenetic Mechanisms in Cerebral Ischemia

“…The role of micro RNAs will not be considered. For comprehensive reviews see Saugstad 39 and Rink and Khanna 40 ).…”

Contributions of central and systemic inflammation to the pathophysiology of Parkinson's disease

“…Although microRNAs (miRNAs) are expressed in the brain, only a limited number of studies have examined the biological role of miRNAs in brain disorders including PD (Hebert and De Strooper, 2007;Saugstad, 2010). These small RNA molecules (21-23 nucleotides) are non-protein coding transcripts that play an important function in post-transcriptional regulation of gene expression in the development, function and survival of mammalian midbrain dopaminergic neurons, and so their expression may be a potential therapeutic marker for disease progression of PD.…”

Loss of MicroRNA-7 Regulation Leads to α-Synuclein Accumulation and Dopaminergic Neuronal Loss In Vivo

“…Aberrant miR activity has been associated with a number of neurodegenerative diseases including PD. [25][26][27][28] In particular, miR-7 has been shown to bind to the 3'UTR of the SNCA gene and inhibit its translation. 29,30 However, the pathophysiological relevance of the miR-7 targeting of SNCA to PD remains unclear.…”