نتایج جستجو برای: lrrk2 inhibitors

تعداد نتایج: 189958  

Journal: :Human molecular genetics 2007
Andrew B West Darren J Moore Catherine Choi Shaida A Andrabi Xiaojie Li Dustin Dikeman Saskia Biskup Zhenshui Zhang Kah-Leong Lim Valina L Dawson Ted M Dawson

Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) cause late-onset Parkinson's disease indistinguishable from idiopathic disease. The mechanisms whereby missense alterations in the LRRK2 gene initiate neurodegeneration remain unknown. Here, we demonstrate that seven of 10 suspected familial-linked mutations result in increased kinase activity. Functional and disease-associated mutation...

Journal: :Neurobiology of disease 2014
Laurie H Sanders Josée Laganière Oliver Cooper Sally K Mak B Joseph Vu Y Anne Huang David E Paschon Malini Vangipuram Ramya Sundararajan Fyodor D Urnov J William Langston Philip D Gregory H Steve Zhang J Timothy Greenamyre Ole Isacson Birgitt Schüle

Parkinson's disease associated mutations in leucine rich repeat kinase 2 (LRRK2) impair mitochondrial function and increase the vulnerability of induced pluripotent stem cell (iPSC)-derived neural cells from patients to oxidative stress. Since mitochondrial DNA (mtDNA) damage can compromise mitochondrial function, we examined whether LRRK2 mutations can induce damage to the mitochondrial genome...

Journal: :Human molecular genetics 2014
Dario C Angeles Patrick Ho Ling Ling Chua Cheng Wang Yan Wann Yap Cheehoe Ng Zhi dong Zhou Kah-Leong Lim Zbigniew K Wszolek Hong Y Wang Eng King Tan

Mutations in leucine-rich repeat kinase 2 (LRRK2) are common causes of familial Parkinson's disease (PD). LRRK2 has been shown to bind peroxiredoxin-3 (PRDX3), the most important scavenger of hydrogen peroxide in the mitochondria, in vitro. Here, we examined the interactions of LRRK2 and PRDX3 in Drosophila models by crossing transgenic LRRK2 and PRDX3 flies. As proof of principle experiments, ...

Journal: :PLoS ONE 2009
Xiaodong Ding Matthew S. Goldberg

Dominantly inherited mutations in the leucine-rich repeat kinase 2 gene (LRRK2) are the most common cause of familial Parkinson's disease (PD) and have also been identified in individuals with sporadic PD. Although the exact cellular function of LRRK2 remains unknown, most PD-linked mutations appear to be toxic to cells in culture via mechanisms that depend on the kinase activity of LRRK2 or on...

2009
Cíntia Barros Santos-Rebouças Cláudia Bueno Abdalla Paloma Águia Martins Fábio José Rodrigues Baldi Jussara Mendonça Santos Luciana Branco Motta Margarete Borges de Borges Dorotéia Rossi Silva Souza Marcela Augusta de Souza Pinhel Jerson Laks Márcia Mattos Gonçalves Pimentel

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene have emerged as a potential common cause for both sporadic and familial Parkinson's Disease (PD) in different populations. The pleomorphic features exhibited by LRRK2 mutation carriers and the central role of Lrrk2 protein in the proper functioning of central nervous system suggest that mutations in this protein might be involved in mul...

Journal: :Proceedings of the National Academy of Sciences of the United States of America 2010
Youren Tong Hiroo Yamaguchi Emilie Giaime Scott Boyle Raphael Kopan Raymond J Kelleher Jie Shen

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson's disease. LRRK2 is a large protein containing a small GTPase domain and a kinase domain, but its physiological role is unknown. To identify the normal function of LRRK2 in vivo, we generated two independent lines of germ-line deletion mice. The dopaminergic system of LRRK2(-/-) mice appears normal,...

2014
Bernard M. H. Law Victoria A. Spain Veronica H. L. Leinster Ruth Chia Alexandra Beilina Hyun J. Cho Jean-Marc Taymans Mary K. Urban Rosa M. Sancho Marian Blanca Ramírez Saskia Biskup Veerle Baekelandt Huaibin Cai Mark R. Cookson Daniel C. Berwick Kirsten Harvey

Mutations in LRRK2, encoding the multifunctional protein leucine-rich repeat kinase 2 (LRRK2), are a common cause of Parkinson disease. LRRK2 has been suggested to influence the cytoskeleton as LRRK2 mutants reduce neurite outgrowth and cause an accumulation of hyperphosphorylated Tau. This might cause alterations in the dynamic instability of microtubules suggested to contribute to the pathoge...

Journal: :Human molecular genetics 2012
João Paulo L Daher Olga Pletnikova Saskia Biskup Alessandra Musso Sandra Gellhaar Dagmar Galter Juan C Troncoso Michael K Lee Ted M Dawson Valina L Dawson Darren J Moore

Mutations in the genes encoding LRRK2 and α-synuclein cause autosomal dominant forms of familial Parkinson's disease (PD). Fibrillar forms of α-synuclein are a major component of Lewy bodies, the intracytoplasmic proteinaceous inclusions that are a pathological hallmark of idiopathic and certain familial forms of PD. LRRK2 mutations cause late-onset familial PD with a clinical, neurochemical an...

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