Department of Medical Neurobiology, Hebrew University-Hadassah Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Neurodegener Dis. 2012;10(1-4):203-6. doi: 10.1159/000332598. Epub 2011 Dec 9.
Parkinson's disease (PD) is the second most frequent neurodegenerative disease worldwide. Clinical diagnosis can only be made when the vast majority of the dopaminergic cell population has died. However, the cause(s) for sporadic PD is/are yet unclear. Transcript changes have recently been described in PD patients' whole blood cells, but corresponding splicing patterns remained unknown.
To search for alternative splicing aberrations in PD patients' blood leukocytes.
We applied exon microarrays to profile PD patients' blood leukocyte mRNA. Exon level splicing analysis served as a basis for downstream classification and functional analyses.
Patients and carefully matched controls were classified by the splicing exon profiles of their leukocyte transcripts. Specifically, many exons were downregulated in PD patients compared to controls. Functional analysis highlighted aberrant splicing of PD-related transcripts and impaired NF-κB cascade and immune response.
PD patient's blood leukocytes exhibit alternative splicing of numerous transcripts. The aberrant alternative splicing in PD patients' blood cells has potential implications for early diagnosis and future therapeutics.
帕金森病（PD）是全球第二常见的神经退行性疾病。当绝大多数多巴胺能细胞死亡时，才能做出临床诊断。然而，散发性 PD 的病因尚不清楚。最近在 PD 患者的全血细胞中描述了转录本变化，但相应的剪接模式仍不清楚。
在 PD 患者的血液白细胞中寻找剪接异常。
我们应用外显子微阵列对 PD 患者的血液白细胞 mRNA 进行了分析。外显子水平的剪接分析作为下游分类和功能分析的基础。
根据白细胞转录本的剪接外显子谱对患者和精心匹配的对照进行分类。具体来说，与对照组相比，许多外显子在 PD 患者中下调。功能分析突出了与 PD 相关的转录物的剪接异常以及 NF-κB 级联和免疫反应受损。
PD 患者的血液白细胞表现出许多转录物的剪接异常。PD 患者血液细胞中的异常剪接可能对早期诊断和未来的治疗有影响。
