The Role of MicroRNAs in Neurodegenerative Diseases: Implications for Early Detection and Treatment

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs that can posttranscriptionally regulate gene expression in development, differentiation, and in response to various stimuli. Numerous miRNAs are very specifically expressed within the central nervous system suggesting they regulate important brain functions. MiRNAs are also required for the postmitotic survival of neurons, strongly suggesting a crucial role in survival and neuroprotection. The fact that diverse arrays of miRNAs have been reported to be dysregulated in several neurodegenerative diseases implies that they can contribute to pathogenesis. As a group, the global burden of neurodegenerative disease is huge and includes conditions such as Alzheimer's disease and other dementias, for which the numbers are steadily rising with the aging population, as well as communicable diseases caused by prions that are of public health concern. As yet, no drugs to halt or even delay the progression of these diseases are available, and this is a huge focus of global research. The best time for therapeutic intervention would be before significant memory loss and tissue destruction occurs such that interventions to boost cell repair and to promote neuroprotective mechanisms could provide significant health benefits. MicroRNA research promises to further elucidate the pathways, genes, and proteins that contribute to the neurodegenerative process that may serve as potential therapeutic targets. Furthermore, given the evidence of the neuroprotective properties of some miRNAs, these small RNA species may themselves be the focus for drug development. Here, we review recent studies that imply a link between miRNA function and neurodegeneration plus discuss how increased knowledge of miRNAs may be used in diagnosis and treatment of neurodegenerative diseases.

MicroRNA in neurodegenerative drug discovery: the way forward?

“…A survey of the literature reveals numerous miRNAs whose dysregulation is known to be associated with neurodegenerative diseases [5,6]. Perhaps unsurprisingly these miRNAs have been mostly studied for their ability to alter the expression of proteins whose misfolding and accumulation is characteristic of particular neurodegenerative disease pathologies, such as beta-amyloid in AD, the mutant huntingtin protein in HD or proteawe resistant prion protein (PrPSc) in prion diseases.…”

“…Global transcript screening has identified the widespread and profound dysregulation of specific miRNAs in numerous neurodegenerative diseases [5,6]. As master regulators of cellular homeostasis, identifying the networks in which these disease-related miRNAs act will provide information on the pathways that are most crucial for neuronal function and survival.…”

Microdissection and transcriptional profiling

“…In fact, loss of miRNA expression in the brain by inactivation of miRNA processing mediators leads to neurodegeneration in numerous animal models. [48][49][50][51] Evidence linking the deregulation of specific miRNAs to the neurodegenerative processes are becoming increasingly apparent 52,53 which further exemplify the important role miRNAs contribute to neurodegenerative diseases. Very little is known about the role of miRNAs in prion associated neurodegeneration therefore justifying the further use of our LCM samples in order to profile miRNAs from CA1 neurons.…”