Mechanism of Autism Spectrum Disorder and The Involvement of microRNA

Abstract

Autism Spectrum Disorder or ASD refers to a broad range of neurodevelopmental disorder characterised by persistent deficits in social abilities, repetitive behavioural pattern and restricted interest propensity that usually developed throughout childhood. It is referred as spectrum disorder due to its wide variation of subsets that includes several conditions. Autism is referred as spectrum of disorders with wide range of subtypes due to its aetiologically diverse nature. Even each person with ASD within the same subsets may experience a distinct set of strengths and challenges in terms of learning, thoughts and problem-solving ranging from highly skilled to being severely affected. The genesis of it is incompletely comprehensible despite numerous studies have been done to elucidate the pathogenic mechanisms beneath this whole range of impaired neurodevelopmental condition. In this review, literature search was performed with primary focus was given to known mechanism of ASD and specific involvement of microRNA. Given the complexity of ASD with diversity of clinical manifestations, it can be considered as multifactorial aetiopathogenesis disorder that is associated with diverse genetic factors that may also be predisposed by environmental exposures and prenatal factors. Environmental risk factor that may modulate the genetic factors predisposing towards ASD includes advanced parental age, prenatal and perinatal factors, medications and toxic materials exposure. This is supported by epigenetic theory which in other words, the environmental risk factors may increase the tendency for the abnormal genes to be expressed at much earlier stage without changing the primary DNA sequence. Meanwhile, spontaneous de novo mutation and neurobiological factors have been proposed to be the factors contributing to ASD. Currently, there are a lot of studies pivoting on identifying the microRNA involved in dysregulation of gene expression in autistic individuals by microRNA expression profiling. These approaches were able to elucidate the specific microRNAs that involves in regulating gene expression at post-transcriptional level. Subsequent pathway analysis had enabled the understanding of potential mechanisms that lead to ASD. As ASD is a heterogenous disorder in nature, the quest to reveal its definite mechanism is challenging. Genetic, neurobiological and environmental factors were regarded as its main causes. A growing number of reports have supported the involvement of microRNA in the mechanism of ASD. Detection of microRNA in extracellular fluids such as serum, saliva and plasma are the key to identify pathways and processes involved in ASD pathophysiology. Further preclinical validation of these microRNAs target transcripts may be beneficial to support its clinical application. Validated microRNAs may potentially use as non-invasive biomarker in early detection and later on opening up opportunities for future potential therapies for ASD.