MicroRNAs and Target Genes As Biomarkers for the Diagnosis of Early Onset of Parkinson Disease

Abstract

Among the neurodegenerative disorders, Parkinson's disease (PD) ranks as the second most common disorder with a higher prevalence in individuals aged over 60 years old. Younger individuals may also be affected with PD which is known as early onset PD (EOPD). Despite similarities between the characteristics of EOPD and late onset PD (LODP), EOPD patients experience much longer disease manifestations and poorer quality of life. Although some individuals are more prone to have EOPD due to certain genetic alterations, the molecular mechanisms that differentiate between EOPD and LOPD remains unclear. Recent findings in PD patients revealed that there were differences in the genetic profiles of PD patients compared to healthy controls, as well as between EOPD and LOPD patients. There were variants identified that correlated with the decline of cognitive and motor symptoms as well as non-motor symptoms in PD. There were also specific microRNAs that correlated with PD progression, and since microRNAs have been shown to be involved in the maintenance of neuronal development, mitochondrial dysfunction and oxidative stress, there is a strong possibility that these microRNAs can be potentially used to differentiate between subsets of PD patients. PD is mainly diagnosed at the late stage, when almost majority of the dopaminergic neurons are lost. Therefore, identification of molecular biomarkers for early detection of PD is important. Given that miRNAs are crucial in controlling the gene expression, these regulatory microRNAs and their target genes could be used as biomarkers for early diagnosis of PD. In this article, we discussed the genes involved and their regulatory miRNAs, regarding their roles in PD progression, based on the findings of significantly altered microRNAs in EOPD studies. We also discussed the potential of these miRNAs as molecular biomarkers for early diagnosis.

Sensing the Stress: A Role for the UPRmt and UPRam in the Quality Control of Mitochondria

“…The RISC complex can bind to its target mRNA and induce mRNA degradation and consequently the abrogation of protein products (Bartel and Chen, 2004 ). For patients, miRNA applications are now considered as promising targeting strategies against human diseases, among them are cancer (Gabra and Salmena, 2017 ; Shirafkan et al, 2017 ), Parkinson's disease (Arshad et al, 2017 ) and cardiac perturbations (Chen et al, 2017 ). Cytosolic miRNAs have been linked to mitochondrial function, too.…”

Insights into the Effects of Mesenchymal Stem Cell-Derived Secretome in Parkinson’s Disease

“…In PD, a relation between miR-34b/c reduction and the resultant DJ-1 and PARKIN decline in several brain areas was found [ 87 ]. Notably, increased miR-494 and miR-4639-5p levels trigger a direct decrease of DJ-1 protein expression, making dopaminergic neurons more susceptible and predisposed to the PD phenotype [ 88 , 89 ]. Interestingly, it has been recently proposed that MSC-derived secretome can ameliorate different biomarkers of PD pathophysiology, thus suggesting MSC-derived secretome as a promising approach to identify and generate valuable PD biomarkers [ 90 ].…”

Urinary Biomarkers for Neurodegenerative Diseases

“…miRNAs are small non-coding RNAs that regulate the expression of their target genes [60]. Various miRNAs have been reported to alter the expression of genes related to PD such as mitochondria dysfunction, α-synuclein regulation, oxidative stress and neuroinflammation [61]. Their presence in CSF, saliva, plasma and urine promoted the investigation of miRNAs for their biomarker potential for NDDs [3].…”