Read by QxMD icon Read

Leucine repeat rich kinase 2

Yue Ma, Chunquan Zheng, Le Shi
Background: Chronic rhinosinusitis (CRS), commonly divided into CRS with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP) is an inflammatory disease which mechanism remain unclear. Leucine-rich repeat kinase 2 (LRRK2) has been proved to be a negative regulator of inflammation response while its role in pathogenesis of CRS has yet to be revealed. This research study was designed to investigate the relationship between the expression level and biologic role of LRRK2 in CRS. Methods: Expression of LRRK2 mRNA and noncoding repressor of NFAT (NRON) were examined by qRT-PCR...
2018: Clinical and Translational Allergy
Qin Rui, Haibo Ni, Fan Gao, Baoqi Dang, Di Li, Rong Gao, Gang Chen
Leucine-rich repeat kinase 2 (LRRK2) is widely expressed in the brain and exerts neurotoxicity in Parkinson's disease. The p38/Drosha signaling activation has been reported to increase cell death under stress. This study was designed to investigate the potential role and mechanism of LRRK2 in secondary brain injury after traumatic brain injury (TBI). A total of 130 male Sprague-Dawley rats were examined using a weight-drop model of TBI. The rats received the specific LRRK2 inhibitor PF-06447475 or LRRK2 pDNA alone or in combination with Drosha pDNA...
2018: Frontiers in Cellular Neuroscience
Maria Perez Carrion, Francesca Pischedda, Alice Biosa, Isabella Russo, Letizia Straniero, Laura Civiero, Marianna Guida, Christian J Gloeckner, Nicola Ticozzi, Cinzia Tiloca, Claudio Mariani, Gianni Pezzoli, Stefano Duga, Irene Pichler, Lifeng Pan, John E Landers, Elisa Greggio, Michael W Hess, Stefano Goldwurm, Giovanni Piccoli
Mutations in leucine-rich repeat kinase 2 gene ( LRRK2 ) are associated with familial and sporadic Parkinson's disease (PD). LRRK2 is a complex protein that consists of multiple domains, including 13 putative armadillo-type repeats at the N-terminus. In this study, we analyzed the functional and molecular consequences of a novel variant, E193K, identified in an Italian family. E193K substitution does not influence LRRK2 kinase activity. Instead it affects LRRK2 biochemical properties, such as phosphorylation at Ser935 and affinity for 14-3-3ε...
2018: Frontiers in Molecular Neuroscience
Panagiotis S Athanasopoulos, Rolf Heumann, Arjan Kortholt
Mutations in human leucine-rich-repeat kinase 2 (LRRK2) have been found to be the most frequent cause of late-onset Parkinson's Disease (PD). LRRK2 is a large protein with two enzymatic domains, a GTPase and a kinase domain. A cluster of (auto)-phosphorylation sites within the N-terminus of LRRK2 have been shown to be crucial for the localization of LRRK2 and is important for PD pathogenesis. In addition, phosphorylation of sites within the G-domain of the protein affect GTPase activity. Here we discuss the role of these (auto)-phosphorylation sites of LRRK2 and their regulation by phosphatases and upstream kinases...
March 12, 2018: Biological Chemistry
Alexia F Kalogeropulou, Jing Zhao, Marc F Bolliger, Anna Memou, Shreya Narasimha, Tyler P Molitor, William H Wilson, Hardy J Rideout, R Jeremy Nichols
Autosomal dominant, missense mutations in the Leucine Rich Repeat protein Kinase 2 ( LRRK2 ) gene are the most common genetic predisposition to develop Parkinson's disease (PD). LRRK2 kinase activity is increased in several pathogenic mutations [N1437H, R1441C/G/H, Y1699C, G2019S], implicating hyperphosphorylation of a substrate in the pathogenesis of disease. Identification of the downstream targets of LRRK2 is a crucial endeavor in the field to understand LRRK2 pathway dysfunction in disease. We have identified the signaling adapter protein p62/SQSTM1 as a novel endogenous interacting partner and substrate of LRRK2...
March 8, 2018: Biochemical Journal
Qin Chen, Xiaoyan Huang, Renjie Li
Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), as a long chain non-coding RNA (lncRNA), has been reported to be upregulated in Parkinson's disease (PD). However, the mechanisms underlying this process remain unknown. Hence, to investigate the role of MALAT1 in PD, N-methyl-4-phenylpyridinium (MPP+ ) was used to induce PD in vitro in the MN9D dopaminergic neuronal cell line and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to induce PD in vivo in C57BL/6 mice. Quantitative Real-Time PCR (qRT-PCR) and western blot assay showed that the expression levels of MALAT1 and leucine-rich repeat kinase (LRRK2) were increased, and that of miR-205-5p was decreased in the midbrains of mice in which PD was induced by MPTP...
2018: American Journal of Translational Research
Qian Wang, Furao Liu, Meichao Zhang, Pingting Zhou, Ci Xu, Yanyan Li, Lei Bian, Yuanhua Liu, Yuan Yao, Fei Wang, Yong Fang, Dong Li
Neutrophils are the most important component of the innate immune system. Mechanistic understanding of the mechanism underlying neutrophil differentiation remains elusive. Using genome-wide RNA-seq, we identified genes whose expression is dramatically up-regulated during neutrophil differentiation. Among them is nucleotide-binding leucine-rich repeat and pyrindomain-containing receptor 12 (NLRP12), which plays a role in immune inflammatory responses. Genetic ablation of NLRP12 suppresses NF-κB inducing kinase (NIK) stabilization, RelB nuclear translocation and neutrophil differentiation in vitro...
2018: International Journal of Biological Sciences
Miao Yu, Muhammad Arshad, Wenmin Wang, Dongyu Zhao, Li Xu, Linkang Zhou
BACKGROUND: Several mutations in leucine rich repeat kinase 2 (LRRK2) gene have been associated with pathogenesis of Parkinson's disease (PD), a neurodegenerative disorder marked by resting tremors, and rigidity, leading to Postural instability. It has been revealed that mutations that lead to an increase of kinase activity of LRRK2 protein are significantly associated with PD pathogenesis. Recent studies have shown that some Rab GTPases, especially Rab8, serve as substrates of LRRK2 and undergo phosphorylation in its switch II domain upon interaction...
February 27, 2018: Lipids in Health and Disease
Kelsey Lee, Khanh-Dung Nguyen, Chao Sun, Mei Liu, Faria Zafar, Jimmy Saetern, Adrian Flierl, James W Tetrud, J William Langston, Dennis Dickson, Birgitt Schüle
BACKGROUND: Mutations in the leucine rich repeat kinase 2 (LRRK2) gene are among the most common genetic causes of Lewy body Parkinson's disease (PD). However, LRRK2 mutations can also lead to a variety of pathological phenotypes other than typical PD, including relatively pure nigrostriatal cell loss without alpha-synuclein-positive Lewy bodies or Lewy neurites, progressive supranuclear palsy (PSP), and multiple system atrophy (MSA). The mechanisms behind this remarkable pleomorphic pathology are currently unclear...
2018: Journal of Parkinson's Disease
Rubén Fernández-Santiago, Alicia Garrido, Jon Infante, Isabel González-Aramburu, María Sierra, Manel Fernández, Francesc Valldeoriola, Esteban Muñoz, Yaroslau Compta, María-José Martí, José Ríos, Eduardo Tolosa, Mario Ezquerra
OBJECTIVES: A recent study showed that Arab-Berbers GG homozygous at rs2421947(C/G) in the dynamin 3 gene (DNM3) had 12.5 years earlier age at onset of leucine-rich repeat kinase 2 (LRRK2)-associated Parkinson's disease (PD) (L2PD). We explored whether this variant modulates the L2PD age at onset in Spain. METHODS: We genotyped rs2421947 in 329 participants (210 L2PD patients, 119 L2PD nonmanifesting p.G2019S carriers), and marker rs356219 (A/G) in the α-synuclein gene (SNCA)...
February 23, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
Qin Rui, Haibo Ni, Di Li, Rong Gao, Gang Chen
The leucine-rich repeat kinase 2 (LRRK2) gene and α-synuclein gene (SNCA) are the key influence factors of Parkinson's disease (PD). It is reported that dysfunction of LRRK2 may influence the accumulation of α-synuclein and its pathology to alter cellular functions and signaling pathways by the kinase activation of LRRK2. The accumulation of α-synuclein is one of the main stimulants of microglias acitiviton. Microglias are macrophages resided in the brain, and activation of microglials is believed to contribute to neuroinflammation and neuronal death in PD...
February 22, 2018: Current Neuropharmacology
Alicia Yoke Wei Wong, Vasilis Oikonomou, Giuseppe Paolicelli, Antonella De Luca, Marilena Pariano, Jan Fric, Hock Soon Tay, Paola Ricciardi-Castagnoli, Teresa Zelante
The Parkinson's disease-associated protein, Leucine-rich repeat kinase 2 (LRRK2), a known negative regulator of nuclear factor of activated T cells (NFAT), is expressed in myeloid cells such as macrophages and dendritic cells (DCs) and is involved in the host immune response against pathogens. Since, the Ca2+ /NFAT/IL-2 axis has been previously found to regulate DC response to the fungus Aspergillus , we have investigated the role played by the kinase LRRK2 during fungal infection. Mechanistically, we found that in the early stages of the non-canonical autophagic response of DCs to the germinated spores of Aspergillus , LRRK2 undergoes progressive degradation and regulates NFAT translocation from the cytoplasm to the nucleus...
2018: Frontiers in Immunology
Nasia Antoniou, Dimitrios Vlachakis, Anna Memou, Emmanouela Leandrou, Polytimi-Eleni Valkimadi, Katerina Melachroinou, Diane B Re, Serge Przedborski, William T Dauer, Leonidas Stefanis, Hardy J Rideout
In experimental models, both in vivo and cellular, over-expression of Parkinson's linked mutant leucine-rich repeat kinase 2 (LRRK2) is sufficient to induce neuronal death. While several cell death associated proteins have been linked to LRRK2, either as protein interactors or as putative substrates, characterization of the neuronal death cascade remains elusive. In this study, we have mapped for the first time the domain within LRRK2 that mediates the interaction with FADD, thereby activating the molecular machinery of the extrinsic death pathway...
February 22, 2018: Scientific Reports
Ning Yuan, Shuangrong Yuan, Zhigang Li, Man Zhou, Peipei Wu, Qian Hu, Liangjiang Wang, Venugopal Mendu, Hong Luo
Protein kinases play fundamental roles in plant development and environmental stress responses. Here, we identified the STRESS INDUCED FACTOR (SIF) gene family, which encodes four leucine-rich repeat receptor-like protein kinases (LRR-RLKs) in Arabidopsis thaliana. The four genes, SIF1-4, are clustered in the genome and highly conserved, but have temporally and spatially distinct expression patterns. We employed Arabidopsis SIF knockout mutants and overexpression transgenics to examine SIF involvement during plant pathogen defense...
February 20, 2018: Plant Physiology
Lei Wang, Elias Einig, Marilia Almeida-Trapp, Markus Albert, Judith Fliegmann, Axel Mithöfer, Hubert Kalbacher, Georg Felix
The discovery in tomato of systemin, the first plant peptide hormone1,2 , was a fundamental change for the concept of plant hormones. Numerous other peptides have since been shown to play regulatory roles in many aspects of the plant life, including growth, development, fertilization and interactions with symbiotic organisms3-6 . Systemin, an 18 amino acid peptide derived from a larger precursor protein7 , was proposed to act as the spreading signal that triggers systemic defence responses observed in plants after wounding or attack by herbivores1,7,8 ...
February 19, 2018: Nature Plants
Andrea C Klaver, Mary P Coffey, Jan O Aasly, David A Loeffler
Lysosome-associated membrane glycoprotein 2 (lamp2) plays critical roles in chaperone-mediated autophagy (CMA) and macroautophagy. Its isoform lamp2a is decreased in Parkinson's disease (PD) substantia nigra. Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most known common cause of late-onset PD; although LRRK2 is thought to regulate macroautophagy, the influence of LRRK2 mutations on lamp2 concentrations in the CNS is unknown. To examine this issue we compared lamp2 levels in cerebrospinal fluid (CSF) between sporadic PD (sPD) patients (n = 31), LRRK2 PD patients (n = 20), and healthy control subjects with or without LRRK2 mutations (LRRK2 CTL = 30, CTL = 27)...
March 15, 2018: Brain Research
Ga Ram Jeong, Eun-Hae Jang, Jae Ryul Bae, Soyoung Jun, Ho Chul Kang, Chi-Hu Park, Joo-Ho Shin, Yukio Yamamoto, Keiko Tanaka-Yamamoto, Valina L Dawson, Ted M Dawson, Eun-Mi Hur, Byoung Dae Lee
BACKGROUND: Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial and sporadic Parkinson's disease (PD). Elevated kinase activity is associated with LRRK2 toxicity, but the substrates that mediate neurodegeneration remain poorly defined. Given the increasing evidence suggesting a role of LRRK2 in membrane and vesicle trafficking, here we systemically screened Rab GTPases, core regulators of vesicular dynamics, as potential substrates of LRRK2 and investigated the functional consequence of such phosphorylation in cells and in vivo...
February 13, 2018: Molecular Neurodegeneration
Cyrille Saintenac, Wing-Sham Lee, Florence Cambon, Jason J Rudd, Robert C King, William Marande, Stephen J Powers, Hélène Bergès, Andy L Phillips, Cristobal Uauy, Kim E Hammond-Kosack, Thierry Langin, Kostya Kanyuka
Deployment of fast-evolving disease-resistance genes is one of the most successful strategies used by plants to fend off pathogens1,2. In gene-for-gene relationships, most cloned disease-resistance genes encode intracellular nucleotide-binding leucine-rich-repeat proteins (NLRs) recognizing pathogen-secreted isolate-specific avirulence (Avr) effectors delivered to the host cytoplasm3,4. This process often triggers a localized hypersensitive response, which halts further disease development 5 . Here we report the map-based cloning of the wheat Stb6 gene and demonstrate that it encodes a conserved wall-associated receptor kinase (WAK)-like protein, which detects the presence of a matching apoplastic effector6-8 and confers pathogen resistance without a hypersensitive response 9 ...
February 12, 2018: Nature Genetics
Sayan Chakraborty, Haiyun Pan, Qingyu Tang, Colin Woolard, Guozhou Xu
During reproduction in flowering plants, the male gametophyte delivers an immotile male gamete to the female gametophyte in the pistil by formation of pollen tubes. In Arabidopsis thaliana, two synergid cells situated on either side of the egg cell produce cysteine-rich chemoattractant peptide LURE that guides the pollen tube to the female gametophyte for sexual reproduction. Recently, in Arabidopsis thaliana, Pollen Receptor Kinase 3 (PRK3), along with PRK1, PRK6, and PRK8, have been predicted to be the receptors responsible for sensing LURE...
February 12, 2018: Scientific Reports
Ana Marote, Yuriy Pomeshchik, Anna Collin, Stefano Goldwurm, Nuno J Lamas, Luísa Pinto, António J Salgado, Laurent Roybon
The leucine-rich repeat kinase 2 (LRRK2) p.G2019S mutation is the most common genetic cause of Parkinson's disease (PD). An induced pluripotent stem cell (iPSC) line CSC-41 was generated from a 75-year old patient diagnosed with PD caused by a p.G2019S mutation in LRRK2. Skin fibroblasts were reprogrammed using a non-integrating Sendai virus-based technology to deliver OCT3/4, SOX2, c-MYC and KLF4 transcription factors. The generated iPSC line exhibits expression of common pluripotency markers, differentiates into the three germ layers and has a normal karyotype...
February 2, 2018: Stem Cell Research
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"