نتایج جستجو برای: lrrk2 inhibitors

تعداد نتایج: 189958  

2015
Wambui S. Wandu Cuiyan Tan Osato Ogbeifun Barbara P. Vistica Guangpu Shi Samuel J. H. Hinshaw Chengsong Xie Xi Chen Dennis M. Klinman Huaibin Cai Igal Gery Elisa Greggio

BACKGROUND Mutations in LRRK2 are related to certain forms of Parkinson's disease and, possibly, to the pathogenesis of Crohn's disease. In both these diseases inflammatory processes participate in the pathogenic process. LRRK2 is expressed in lymphoid cells and, interestingly, Lrrk2 (-/-) mice were reported to develop more severe experimental colitis than their wild type (WT) controls. Here, w...

2016
Vinicius M. Fava Jérémy Manry Aurélie Cobat Marianna Orlova Nguyen Van Thuc Nguyen Ngoc Ba Vu Hong Thai Laurent Abel Alexandre Alcaïs Erwin Schurr Christian Johnson

BACKGROUND Depending on the epidemiological setting, a variable proportion of leprosy patients will suffer from excessive pro-inflammatory responses, termed type-1 reactions (T1R). The LRRK2 gene encodes a multi-functional protein that has been shown to modulate pro-inflammatory responses. Variants near the LRRK2 gene have been associated with leprosy in some but not in other studies. We hypoth...

2013
Florian Giesert Andreas Hofmann Alexander Bürger Julia Zerle Karina Kloos Ulrich Hafen Luise Ernst Jingzhong Zhang Daniela Maria Vogt-Weisenhorn Wolfgang Wurst

Missense mutations in the leucine-rich repeat kinase 2 gene (LRRK2) are linked to autosomal dominant forms of Parkinson's disease (PD). In order to get insights into the physiological role of Lrrk2, we examined the distribution of Lrrk2 mRNA and different splice variants in the developing murine embryo and the adult brain of Mus musculus. To analyse if the Lrrk2-paralog, Lrrk1, may have redunda...

2014
Pika Miklavc Konstantin Ehinger Kristin E. Thompson Nina Hobi Derya R. Shimshek Manfred Frick

Leucine-rich repeat kinase 2 (LRRK2) is known to play a role in the pathogenesis of various diseases including Parkinson disease, morbus Crohn, leprosy and cancer. LRRK2 is suggested to be involved in a number of cell biological processes such as vesicular trafficking, transcription, autophagy and lysosomal pathways. Recent histological studies of lungs of LRRK2 knock-out (LRRK2 -/-) mice revea...

Journal: :Human molecular genetics 2013
Hyun Jin Cho Guoxiang Liu Seok Min Jin Loukia Parisiadou Chengsong Xie Jia Yu Lixin Sun Bo Ma Jinhui Ding Renée Vancraenenbroeck Evy Lobbestael Veerle Baekelandt Jean-Marc Taymans Ping He Juan C Troncoso Yong Shen Huaibin Cai

Recent genome-wide association studies indicate that a simple alteration of Leucine-rich repeat kinase 2 (LRRK2) gene expression may contribute to the etiology of sporadic Parkinson's disease (PD). However, the expression and regulation of LRRK2 protein in the sporadic PD brains remain to be determined. Here, we found that the expression of LRRK2 protein was enhanced in the sporadic PD patients...

Journal: :BMC Medicine 2008
Jeanne C Latourelle Mei Sun Mark F Lew Oksana Suchowersky Christine Klein Lawrence I Golbe Margery H Mark John H Growdon G Frederick Wooten Ray L Watts Mark Guttman Brad A Racette Joel S Perlmutter Anwar Ahmed Holly A Shill Carlos Singer Stefano Goldwurm Gianni Pezzoli Michela Zini Marie H Saint-Hilaire Audrey E Hendricks Sally Williamson Michael W Nagle Jemma B Wilk Tiffany Massood Karen W Huskey Jason M Laramie Anita L DeStefano Kenneth B Baker Ilia Itin Irene Litvan Garth Nicholson Alastair Corbett Martha Nance Edward Drasby Stuart Isaacson David J Burn Patrick F Chinnery Peter P Pramstaller Jomana Al-hinti Anette T Moller Karen Ostergaard Scott J Sherman Richard Roxburgh Barry Snow John T Slevin Franca Cambi James F Gusella Richard H Myers

BACKGROUND We report age-dependent penetrance estimates for leucine-rich repeat kinase 2 (LRRK2)-related Parkinson's disease (PD) in a large sample of familial PD. The most frequently seen LRRK2 mutation, Gly2019Ser (G2019S), is associated with approximately 5 to 6% of familial PD cases and 1 to 2% of idiopathic cases, making it the most common known genetic cause of PD. Studies of the penetran...

2015
Claudia Manzoni Paul Denny Ruth C. Lovering Patrick A. Lewis

LRRK2 was identified in 2004 as the causative protein product of the Parkinson's disease locus designated PARK8. In the decade since then, genetic studies have revealed at least 6 dominant mutations in LRRK2 linked to Parkinson's disease, alongside one associated with cancer. It is now well established that coding changes in LRRK2 are one of the most common causes of Parkinson's. Genome-wide as...

2010
Pooja P. Pungaliya Yuchen Bai Kerri Lipinski Vasanti S. Anand Saurabh Sen Eugene L. Brown Brian Bates Peter H. Reinhart Andrew B. West Warren D. Hirst Steven P. Braithwaite

Mutations in LRRK2 (leucine-rich repeat kinase 2) have been identified as major genetic determinants of Parkinson's disease (PD). The most prevalent mutation, G2019S, increases LRRK2's kinase activity, therefore understanding the sites and substrates that LRRK2 phosphorylates is critical to understanding its role in disease aetiology. Since the physiological substrates of this kinase are unknow...

Journal: :Proceedings of the National Academy of Sciences of the United States of America 2005
Wanli W Smith Zhong Pei Haibing Jiang Darren J Moore Yideng Liang Andrew B West Valina L Dawson Ted M Dawson Christopher A Ross

Parkinson's disease (PD) is a disorder of movement, cognition, and emotion, and it is characterized pathologically by neuronal degeneration with Lewy bodies, which are cytoplasmic inclusion bodies containing deposits of aggregated proteins. Most PD cases appear to be sporadic, but genetic forms of the disease, caused by mutations in alpha-synuclein, parkin, and other genes, have helped elucidat...

Journal: :EMBO reports 2015
Andrea M A Schreij Mathilde Chaineau Wenjing Ruan Susan Lin Philip A Barker Edward A Fon Peter S McPherson

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of dominant-inherited Parkinson's disease (PD), and yet we do not fully understand the physiological function(s) of LRRK2. Various components of the clathrin machinery have been recently found mutated in familial forms of PD. Here, we provide molecular insight into the association of LRRK2 with the clathrin machinery. W...

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