Abstract
Neurodegenerative disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and frontotemporal dementias (FTD), are considered distinct entities, however, there is increasing evidence of an overlap from the clinical, pathological and genetic points of view. All neurodegenerative diseases are characterized by neuronal loss and death in specific areas of the brain, for example, hippocampus and cortex for AD, midbrain for PD, frontal and temporal lobes for FTD. Loss of neurons is a relatively late event in the progression of neurodegenerative diseases that is typically preceded by other events such as metabolic changes, synaptic dysfunction and loss, neurite retraction, and the appearance of other abnormalities, such as axonal transport defects. The brain’s ability to compensate for these dysfunctions occurs over a long period of time and results in late clinical manifestation of symptoms, when successful pharmacological intervention is no longer feasible. Currently, diagnosis of AD, PD and different forms of dementia is based primarily on analysis of the patient’s cognitive function. It is therefore important to find non-invasive diagnostic methods useful to detect neurodegenerative diseases during early, preferably asymptomatic stages, when a pharmacological intervention is still possible. Altered expression of microRNAs (miRNAs) in many disease states, including neurodegeneration, and increasing relevance of miRNAs in biofluids in different pathologies has prompted the study of their possible application as neurodegenerative diseases biomarkers in order to identify new therapeutic targets. Here, we review what is known about the role of miRNAs in the pathogenesis of neurodegeneration and the possibilities and challenges of using these small RNA molecules as a signature for neurodegenerative conditions.
Highlights
IntroductionMicroRNAs (miRNAs) are a family of short, single-stranded 21-22 nucleotides-long non-coding
MicroRNAs are a family of short, single-stranded 21-22 nucleotides-long non-codingRNAs, constituting about 1% of all human genes and the most abundant class of small RNAs in animals
Tremendous efforts have been made in recent years to identify the neuropathological, biochemical, and genetic biomarkers of the diseases so that the diagnosis could be established in the earlier stages
Summary
MicroRNAs (miRNAs) are a family of short, single-stranded 21-22 nucleotides-long non-coding. Pre-miRNA is exported into the cytoplasm by Exportin-5 (Exp5) in complex with Ran-GTP and once in the cytoplasm, it is processed by Dicer, that creates a mature miRNAs duplex of approximately 22 bp length [16,17] It is separated into the functional guide strand, which is complementary to the target, and the passenger strand, which is subsequently degraded. MiRNAs in the Nervous System miRNAs are found in high abundance within the nervous system where they often display a brain-specific expression pattern and are usually found to be co-expressed with their targets They act as key regulators of different biological functions including synaptic plasticity and neurogenesis, in which they channelize the cellular physiology toward neuronal differentiation. A causal link between a specific miRNA and a disease has been established in just a few cases, and most of the mechanistic data originates from invertebrate model systems
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