12th International Congress of Parkinson's Disease and Movement Disorders
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Chicago, IL, USA
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Objective: To elucidate physiological function of LRRK2 is important for understanding the molecular etiology of PARK8, and of idiopathic Parkinson’s disease as well. We examined alteration in the levels of the LRRK2 protein during a developmental period of the mouse brain.
Background: A hereditary form of Parkinson’s disease, PARK8, was first found and mapped the gene to chromosome 12p11.2-q13.1 in a family of Japan by Dr. Hasegawa and her colleagues (Funayama et al. 2002). In 2004, the causative gene for PARK8 was identified as leucine-rich repeat kinase 2 (LRRK2) / dardarin. The LRRK2 protein is consisted of several highly conserved functional domains including a leacine-rich repeat protein-protein interaction motif, a Rab-like small GTPase domain, and a mixed-lineage kinase-like domain. Several reports suggest that the disease causing mutations may affect the kinase activity of LRRK2.
Methods: We expressed and purified the kinase domain in E.coli as a GST fusion protein, and the purified protein was immunized to rabbits to raise a specific antibody. We used the antibody to see the developmental change of LRRK2 protein in the mouse brain by Western blot analysis.
Results: The antibody recognized a protein band around 280-kDa in a homogenate of COS-1 cells transected with a full-length of human LRRK2 cDNA. The 280-kDa protein band was gradually increased in the mouse brain from E17 (embryonic day 17), P1 (post-natal day 1), P6, to adult, when the same amount of the protein was loaded on the gel. At E17 and P1, we detected a protein band at higher-molecular weight over 280-kDa, implying presence of an isoform of LRRK2 in embryos. We also detected the other protein bands at 40-kDa and 70-kDa.
Conclusions: Alteration in the protein amount and in the profile of LRRK2 by an Western blot analysis may suggest an important physiological role of LRRK2 in development of neurons.
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