Circulating microRNAs in Neurodegenerative Diseases

Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), are caused by a combination of events that impair normal neuronal function. Although they are considered different disorders, there are overlapping features among them from the clinical, pathological, and genetic points of view. Synaptic dysfunction and loss, neurite retraction, and the appearance of other abnormalities such as axonal transport defects normally precede the neuronal loss that is a relatively late event. The diagnosis of many neurodegenerative diseases is mainly based on patient's cognitive function analysis, and the development of diagnostic methods is complicated by the brain's capacity to compensate for neuronal loss over a long period of time. This results in the late clinical manifestation of symptoms, a time when successful treatment is no longer feasible. Thus, a noninvasive diagnostic method based on early events detection is particularly important. In the last years, some biomarkers expressed in human body fluids have been proposed. microRNAs (miRNAs), with their high stability, tissue- or cell type-specific expression, lower cost, and shorter time in the assay development, could constitute a good tool to obtain an early disease diagnosis for a wide number of human pathologies, including neurodegenerative diseases. The possibilities and challenges of using these small RNA molecules as a signature for neurodegenerative disorders is a highly promising approach for developing minimally invasive screening tests and to identify new therapeutic targets.