miR-34a in Neurophysiology and Neuropathology

Epigenetic influence of brain and neuronal function plays key regulatory roles in health and diseases. The microRNA miR-34a is a tumor suppressor transcript, and its loss has been prominently linked to various human cancers, including malignancies of the brain. Interestingly, miR-34a is abundantly expressed in the adult mammalian brain, and emerging evidence has implicated its involvement in a range of neurodevelopmental and neuropathological processes. Developmentally, miR-34a regulates neural stem/progenitor cell differentiation and aspects of neurogenesis. During aging, its elevation is connected to hearing loss and age-related macular degeneration. Pathologically, its elevations during epileptic seizures and ischemic stroke contribute to neuronal injury and death. Inhibition or suppression of miR-34a improved neuronal survival against a variety of neurotoxins implicated in Parkinson's disease. Its elevation may also play a role in neuronal demise in animal models of Alzheimer's disease, and suppression of its levels may be generally neuroprotective. The roles and activities of miR-34a in the brain are modulated by factors that control its expression (such as Tp53/73), as well as its downstream target genes (such as the sirtuins SIRT1 and SIRT6) and signaling pathways (such the Notch pathway). We discuss here the known and emerging roles of the miR-34a regulatory network in neurophysiology and neuropathology.