Mata Ignacio F, Wedemeyer William J, Farrer Matthew J, Taylor Julie P, Gallo Kathleen A
Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL 32224, USA.
Trends Neurosci. 2006 May;29(5):286-93. doi: 10.1016/j.tins.2006.03.006. Epub 2006 Apr 17.
Parkinson's disease (PD) is the most common motor neurodegenerative disease. Mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) have been linked recently with autosomal-dominant parkinsonism that is clinically indistinguishable from typical, idiopathic, late-onset PD. Thus, the protein LRRK2 has emerged as a promising therapeutic target for treatment of PD. LRRK2 is extraordinarily large and complex, with multiple enzymatic and protein-interaction domains, each of which is targeted by pathogenic mutations in familial PD. This review places the PD-associated mutations of LRRK2 in a structural and functional framework, with the ultimate aim of deciphering the molecular basis of LRRK2-associated pathogenesis. This, in turn, should advance our understanding and treatment of familial and idiopathic PD.
帕金森病（PD）是最常见的运动性神经退行性疾病。富含亮氨酸重复激酶2（LRRK2）编码基因的突变最近与常染色体显性帕金森综合征相关，该综合征在临床上与典型的、特发性的、晚发性帕金森病无法区分。因此，LRRK2蛋白已成为治疗帕金森病的一个有前景的治疗靶点。LRRK2非常庞大且复杂，具有多个酶促和蛋白质相互作用结构域，每个结构域都是家族性帕金森病中致病突变的靶点。本综述将LRRK2与帕金森病相关的突变置于结构和功能框架中，最终目的是破译LRRK2相关发病机制的分子基础。反过来，这应该会促进我们对家族性和特发性帕金森病的理解和治疗。
