Mushtaq Gohar, Greig Nigel H, Anwar Firoz, Zamzami Mazin A, Choudhry Hani, Shaik Munvar M, Tamargo Ian A, Kamal Mohammad A
Drug Design and Development Section, Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Med Chem. 2016;12(3):217-25. doi: 10.2174/1573406411666151030112140.
Detection of biomarkers for neurodegenerative disorders (NDDs) within brain tissues of Alzheimer's disease (AD) and Parkinson's disease (PD) patients has always been hampered by our inability to access and biopsy tissue of key brain regions implicated in disease occurrence and progression. Currently, diagnosis of NDDs is principally based on clinical observations of symptoms that present at later stages of disease progression, followed by neuroimaging and, possibly, CSF evaluation. One way to potentially detect and diagnose NDDs at a far earlier stage is to screen for abnormal levels of specific disease markers within the peripheral circulation of patients with NDDs. Increasing evidence suggests that there is dysregulation of microRNAs (miRNAs) in NDDs. Peripheral blood mononuclear cells, as well as biofluids, such as plasma, serum, urine and cerebrospinal fluid, contain miRNAs that can be identified and quantified. Circulating miRNAs within blood and other biofluids may thus be characterized and used as non-invasive, diagnostic biomarkers that facilitate the early detection of disease and potentially the continual monitoring of disease progression for NDDs such as AD and PD. Plainly, such a screen is only possible with a clear understanding of which miRNAs change with disease, and when these changes occur during the progression of AD and PD. Such information is becoming increasingly available and, in the near future, may not only support disease diagnosis, but provide the opportunity to evaluate therapeutic interventions earlier in the disease process.
在阿尔茨海默病(AD)和帕金森病(PD)患者的脑组织中检测神经退行性疾病(NDDs)的生物标志物,一直受到我们无法获取和活检与疾病发生和进展相关的关键脑区组织的阻碍。目前,NDDs的诊断主要基于疾病进展后期出现的症状的临床观察,随后进行神经影像学检查,可能还包括脑脊液评估。一种有可能在更早阶段检测和诊断NDDs的方法是筛查NDDs患者外周循环中特定疾病标志物的异常水平。越来越多的证据表明,NDDs中存在微小RNA(miRNA)的失调。外周血单核细胞以及血浆、血清、尿液和脑脊液等生物流体中都含有可被识别和定量的miRNA。血液和其他生物流体中的循环miRNA因此可以被表征,并用作非侵入性诊断生物标志物,有助于早期检测疾病,并可能对AD和PD等NDDs的疾病进展进行持续监测。显然,只有清楚了解哪些miRNA随疾病变化以及这些变化在AD和PD进展过程中何时发生,这样的筛查才有可能。此类信息越来越容易获取,在不久的将来,不仅可能支持疾病诊断,还能提供在疾病过程早期评估治疗干预措施的机会。