Arshad Ahmad R, Sulaiman Siti A, Saperi Amalia A, Jamal Rahman, Mohamed Ibrahim Norlinah, Abdul Murad Nor Azian
UKM Medical Centre, UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Bandar Tun Razak, Malaysia.
Department of Medicine, Faculty of Medicine, UKM Medical Centre, Universiti Kebangsaan Malaysia, Bandar Tun Razak, Malaysia.
Front Mol Neurosci. 2017 Oct 31;10:352. doi: 10.3389/fnmol.2017.00352. eCollection 2017.
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.
在神经退行性疾病中,帕金森病(PD)是第二常见的疾病,在60岁以上人群中患病率较高。较年轻的个体也可能患帕金森病,即早发性帕金森病(EOPD)。尽管EOPD和晚发性帕金森病(LOPD)的特征有相似之处,但EOPD患者的疾病表现持续时间更长,生活质量更差。虽然一些个体由于某些基因改变更容易患EOPD,但区分EOPD和LOPD的分子机制仍不清楚。帕金森病患者的最新研究结果显示,与健康对照相比,帕金森病患者的基因谱存在差异,EOPD和LOPD患者之间也存在差异。已鉴定出与帕金森病认知、运动症状以及非运动症状的衰退相关的变异。也有与帕金森病进展相关的特定微小RNA,由于微小RNA已被证明参与神经元发育的维持、线粒体功能障碍和氧化应激,这些微小RNA很有可能可用于区分帕金森病患者的亚组。帕金森病主要在晚期被诊断出来,此时几乎大多数多巴胺能神经元已经丧失。因此,鉴定用于早期检测帕金森病的分子生物标志物很重要。鉴于微小RNA在控制基因表达方面至关重要,这些调节性微小RNA及其靶基因可作为帕金森病早期诊断的生物标志物。在本文中,我们根据EOPD研究中显著改变的微小RNA的研究结果,讨论了相关基因及其调节性微小RNA在帕金森病进展中的作用。我们还讨论了这些微小RNA作为早期诊断分子生物标志物的潜力。