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.