Cell Death and Disease
MicroRNAs (miRNAs) play important roles in regulating a plethora of physiological and pathophysiogical processes including neurodegeneration. In both HIV associated dementia in humans and its monkey model SIV encephalitis we find miR-21, a miRNA largely known for its link to oncogenesis, to be significantly upregulated in the brain. In situ hybridization of the diseased brain sections revealed induction of miR-21 in neurons. MiR-21 can be induced in neurons by prolonged N-methyl-D-aspartic acid receptor stimulation, an excitotoxic process active in HIV and other neurodegenerative diseases. Introduction of miR-21 into human neurons leads to pathological functional defects. Furthermore, we show that miR-21 specifically targets the mRNA of myocyte enhancer factor 2C (MEF2C), a transcription factor crucial for neuronal function, and reduces its expression. MEF2C is dramatically downregulated in neurons of HIV-associated dementia patients as well as monkeys with SIVE. Together, this study elucidates a novel role for miR-21 in the brain, not only as a potential signature of neurological disease but also as a crucial effector of HIV induced neuronal dysfunction and neurodegeneration.
Animals, Down-Regulation, HIV Infections, Haplorhini, Humans, MEF2 Transcription Factors, MicroRNAs, Myogenic Regulatory Factors, Neurodegenerative Diseases, Neurons, RNA, Messenger, Receptors, N-Methyl-D-Aspartate, Simian Acquired Immunodeficiency Syndrome
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Yelamanchili, Sowmya V.; Chaudhuri, A Datta; Chen, L N.; Xiong, Huangui; and Fox, Howard S., "MicroRNA-21 dysregulates the expression of MEF2C in neurons in monkey and human SIV/HIV neurological disease." (2010). Journal Articles: Pharmacology & Experimental Neuroscience. 7.