Role of miRNAs in multiple sclerosis: study of miRNAs in cerebrospinal fluid for different clinical conditions

Abstract

Multiple sclerosis (MS) is considered a chronic inflammatory and neurodegenerative disease, characterized by the existence of demyelinated areas in the central nervous system, infiltration of inflammatory cells in the brain parenchyma, gliosis and, axonal damage. The etiology is still unknown but it has been suggested that some epigenetic mechanisms such as microRNAs (miRNAs) are involved in the complex interaction between some genetic and environmental factors producing the pathology and the symptoms in MS. miRNAs might regulate gene expression post-transcriptionally. They also present many properties to be considered as promising biomarkers for different pathological conditions as they could be released into biological fluids. In this doctoral thesis, specific miRNA signatures in different clinical and pre- clinical forms of MS are described. Altogether, miR-21-5p, miR-20a-5p, miR-142-5p, miR-143-3p, miR-146a-5p and miR-448 are proposed as potential miRNA candidates involved in MS pathogenesis as their deregulation has been manifested in different sub-studies

La esclerosis múltiple (EM) es considerada una enfermedad crónica, inflamatoria y neurodegenerativa, caracterizada por la existencia de áreas desmielinizadas en el sistema nervioso central, infiltración de células inflamatorias en el parénquima cerebral, gliosis y daño axonal. La etiología aún se desconoce, pero se cree que diferentes mecanismos epigenéticos como los microRNAs (miRNAs) influyen en la compleja interacción entre factores genéticos y ambientales que producen la patología y los síntomas en la EM. miRNAs son capaces de regular la expresión génica postranscripcionalmente y presentan, a su vez, muchas propiedades para ser considerados potenciales biomarcadores en diferentes condiciones patológicas. En esta tesis doctoral se describen perfiles de miRNAs específicos en diferentes formas clínicas y preclínicas de EM. En resumen, miR-21-5p, miR- 20a-5p, miR-142-5p, miR-143-3p, miR-146a-5p y miR- 448 se proponen como posibles miRNAs candidatos a estar involucrados en la patogénesis de la EM ya que su desregulación se ha observado en diferentes subestudios