نتایج جستجو برای: lrrk2 inhibitors

تعداد نتایج: 189958  

2010
Azad Kumar Elisa Greggio Alexandra Beilina Alice Kaganovich Diane Chan Jean-Marc Taymans Benjamin Wolozin Mark R. Cookson

Mutations in the gene encoding Leucine-rich repeat kinase 2 (LRRK2) are the most common cause of inherited Parkinson's disease (PD). LRRK2 is a multi-domain protein kinase containing a central catalytic core and a number of protein-protein interaction domains. An important step forward in the understanding of both the biology and the pathology of LRRK2 would be achieved by identification of its...

2010
Karina Haebig Christian Johannes Gloeckner Marta Garcia Miralles Frank Gillardon Claudia Schulte Olaf Riess Marius Ueffing Saskia Biskup Michael Bonin

BACKGROUND Mutations within the leucine-rich repeat kinase 2 (LRRK2) gene are a common cause of familial and sporadic Parkinson's disease. The multidomain protein LRRK2 exhibits overall low GTPase and kinase activity in vitro. METHODOLOGY/PRINCIPAL FINDINGS Here, we show that the rho guanine nucleotide exchange factor ARHGEF7 and the small GTPase CDC42 are interacting with LRRK2 in vitro and ...

Journal: :Biochemical Society transactions 2012
Jean-Marc Taymans

LRRK2 (leucine-rich repeat kinase 2) is a large protein encoding multiple functional domains, including two catalytically active domains, a kinase and a GTPase domain. The LRRK2 GTPase belongs to the Ras-GTPase superfamily of GTPases, more specifically to the ROC (Ras of complex proteins) subfamily. Studies with recombinant LRRK2 protein purified from eukaryotic cells have confirmed that LRRK2 ...

2011
Jean-Marc Taymans Renée Vancraenenbroeck Petri Ollikainen Alexandra Beilina Evy Lobbestael Marc De Maeyer Veerle Baekelandt Mark R. Cookson

Leucine rich repeat kinase 2 (LRRK2) is a Parkinson's disease (PD) gene that encodes a large multidomain protein including both a GTPase and a kinase domain. GTPases often regulate kinases within signal transduction cascades, where GTPases act as molecular switches cycling between a GTP bound "on" state and a GDP bound "off" state. It has been proposed that LRRK2 kinase activity may be increase...

2009
Rosa M. Sancho Bernard M.H. Law Kirsten Harvey

Mutations in PARK8, encoding LRRK2, are the most common known cause of Parkinson's disease. The LRRK2 Roc-COR tandem domain exhibits GTPase activity controlling LRRK2 kinase activity via an intramolecular process. We report the interaction of LRRK2 with the dishevelled family of phosphoproteins (DVL1-3), key regulators of Wnt (Wingless/Int) signalling pathways important for axon guidance, synap...

2016
Katerina Melachroinou Emmanouela Leandrou Polytimi-Eleni Valkimadi Anna Memou Georgios Hadjigeorgiou Leonidas Stefanis Hardy J. Rideout

BACKGROUND Despite the plethora of sequence variants in LRRK2, only a few clearly segregate with PD. Even within this group of pathogenic mutations, the phenotypic profile can differ widely. OBJECTIVE We examined multiple properties of LRRK2 behavior in cellular models over-expressing three sequence variants described in Greek PD patients in comparison to several known pathogenic and non-path...

Journal: :The Journal of neuroscience : the official journal of the Society for Neuroscience 2009
Shamol Saha Maria D Guillily Andrew Ferree Joel Lanceta Diane Chan Joy Ghosh Cindy H Hsu Lilach Segal Kesav Raghavan Kunihiro Matsumoto Naoki Hisamoto Tomoki Kuwahara Takeshi Iwatsubo Landon Moore Lee Goldstein Mark Cookson Benjamin Wolozin

Mutations in leucine-rich repeat kinase 2 (LRRK2) cause autosomal-dominant familial Parkinson's disease. We generated lines of Caenorhabditis elegans expressing neuronally directed human LRRK2. Expressing human LRRK2 increased nematode survival in response to rotenone or paraquat, which are agents that cause mitochondrial dysfunction. Protection by G2019S, R1441C, or kinase-dead LRRK2 was less ...

Journal: :Cell 2014
Ian Martin Jungwoo Wren Kim Byoung Dae Lee Ho Chul Kang Jin-Chong Xu Hao Jia Jeannette Stankowski Min-Sik Kim Jun Zhong Manoj Kumar Shaida A. Andrabi Yulan Xiong Dennis W. Dickson Zbigniew K. Wszolek Akhilesh Pandey Ted M. Dawson Valina L. Dawson

Mutations in leucine-rich repeat kinase 2 (LRRK2) are a common cause of familial and sporadic Parkinson's disease (PD). Elevated LRRK2 kinase activity and neurodegeneration are linked, but the phosphosubstrate that connects LRRK2 kinase activity to neurodegeneration is not known. Here, we show that ribosomal protein s15 is a key pathogenic LRRK2 substrate in Drosophila and human neuron PD model...

2015
Yuzuru Imai Yoshito Kobayashi Tsuyoshi Inoshita Hongrui Meng Taku Arano Kengo Uemura Takeshi Asano Kenji Yoshimi Chang-Liang Zhang Gen Matsumoto Toshiyuki Ohtsuka Ryoichiro Kageyama Hiroshi Kiyonari Go Shioi Nobuyuki Nukina Nobutaka Hattori Ryosuke Takahashi Kah-Leong Lim

Leucine-rich repeat kinase 2 (LRRK2) is a key molecule in the pathogenesis of familial and idiopathic Parkinson's disease (PD). We have identified two novel LRRK2-associated proteins, a HECT-type ubiquitin ligase, HERC2, and an adaptor-like protein with six repeated Neuralized domains, NEURL4. LRRK2 binds to NEURL4 and HERC2 via the LRRK2 Ras of complex proteins (ROC) domain and NEURL4, respect...

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