Beilina A, Rudenko IN, Kaganovich A, Civiero L, Chau H, Kalia SK, Kalia LV, Lobbestael E, Chia R, Ndukwe K, Ding J, Nalls MA, International Parkinson’s Disease Genomics Consortium, North American Brain Expression Consortium, Olszewski M, Hauser DN, Kumaran R, Lozano AM, Baekelandt V, Greene LE, Taymans JM, Greggio E, Cookson MR. Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease. Proc Natl Acad Sci U S A. 2014 Feb 18;111(7):2626-31. Epub 2014 Feb 7 PubMed.

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    • User Profile Image Zhenyu Yue
      Icahn School of Medicine at Mount Sinai
    • Posted:

    With increasing numbers of genetic risk factors for PD being identified, critical questions are whether these genes are connected, function in the same cellular pathways, or whether a common pathway exists for the majority of PD cases. Using large-scale screening, the Cookson group found three proteins that interact with LRRK2, an important PD-linked protein kinase. Two of them, Rab7L1 and GAK, were identified as risk factors for PD in previous GWAS studies. The new findings provide insight into functional connectivity of the three PD genes at the molecular level, and suggest a common pathway may be implicated in idiopathic PD. That the same “hits” arise from two completely independent approaches is particularly interesting and extremely valuable in the validation of pathogenic pathways in PD. In fact, the results from Cookson’s group, together with the previous evidence provided by Abeliovich and colleagues for the genetic interaction between Rab7L1 and LRRK2 (MacLeod 2013), open new avenues for the research of pathogenic pathways in more common forms of PD.

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