scholarly journals Cellular effects of LRRK2 mutations

2012 ◽  
Vol 40 (5) ◽  
pp. 1070-1073 ◽  
Author(s):  
Mark R. Cookson
Keyword(s):  
Parkinson’S Disease ◽  
High Expression ◽  
Leucine Rich Repeat ◽  
Common Cause ◽  
Expression Levels ◽  
Neuronal Viability ◽  
Cellular Effects ◽  
Cellular Models ◽  
Discrete Structures ◽  
Cellular Phenotypes

Mutations in LRRK2 (leucine-rich repeat kinase 2) are a relatively common cause of inherited PD (Parkinson's disease), but the mechanism(s) by which mutations lead to disease are poorly understood. In the present paper, I discuss what is known about LRRK2 in cellular models, focusing specifically on assays that have been used to tease apart the effects of LRRK2 mutations on cellular phenotypes. LRRK2 expression has been suggested to cause loss of neuronal viability, although because it also has a strong effect on the length of neurites on these cells, whether this is true toxicity or not is unclear. Also, LRRK2 mutants can promote the redistribution of LRRK2 from diffuse cytosolic staining to more discrete structures, at least at high expression levels achieved in transfection experiments. The relevance of these phenotypes for PD is not yet clear, and a great deal of work is needed to understand them in more depth.

scholarly journals Analysis of the LRRK2 p.G2019S mutation in Colombian Parkinson’s Disease Patients

2015 ◽  
pp. 117-121 ◽  
Author(s):  
Andres Felipe Duque ◽  
Juan Carlos Lopez ◽  
Helena Hernandez ◽  
Bruno Benitez ◽  
Juan Jose Yunis ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson Disease ◽  
Latin American ◽  
Autosomal Dominant ◽  
Late Onset ◽  
Causal Factor ◽  
Leucine Rich Repeat ◽  
Common Cause ◽  
Asymptomatic Control ◽  
Normal Controls

Introduction: Mutations in the leucine-rich repeat kinase 2 gene (LRRK2 or Dardarin) are considered to be a common cause of autosomal dominant and sporadic Parkinson´s disease, but the prevalence of these mutations varies among populations. Objective: to analysed the frequency of the LRRK2 p.G2019S mutation (c.6055G>A transition) in a sample of Colombian patients. Materials and Methods: In the present study we have analysed the frequency of the LRRK2 p.G2019S mutation in 154 patients with familial or sporadic Parkinson Disease, including early and late onset patients, and 162 normal controls. Results: Our results show occurrence of this mutation in two cases (2/154, 1.3%) with classical Parkinson´s signs, and one completely asymptomatic control (1/162, 0.6%). Conclusion: The p.G2019S mutation is not an important causal factor of Parkinson Disease in Colombia having similar frequencies to those reported in other Latin American populations.

scholarly journals Roco Proteins: GTPases with a Baroque Structure and Mechanism

2019 ◽  
Vol 20 (1) ◽  
pp. 147 ◽  
Author(s):  
Lina Wauters ◽  
Wim Versées ◽  
Arjan Kortholt
Keyword(s):  
Parkinson’S Disease ◽  
Recent Work ◽  
Protein Family ◽  
Leucine Rich Repeat ◽  
Working Mechanism ◽  
Ongoing Debate ◽  
Common Cause ◽  
Physiological Functions ◽  
Working Hypothesis ◽  
Domain Protein

Mutations in leucine-rich repeat kinase 2 (LRRK2) are a common cause of genetically inherited Parkinson’s Disease (PD). LRRK2 is a large, multi-domain protein belonging to the Roco protein family, a family of GTPases characterized by a central RocCOR (Ras of complex proteins/C-terminal of Roc) domain tandem. Despite the progress in characterizing the GTPase function of Roco proteins, there is still an ongoing debate concerning the working mechanism of Roco proteins in general, and LRRK2 in particular. This review consists of two parts. First, an overview is given of the wide evolutionary range of Roco proteins, leading to a variety of physiological functions. The second part focusses on the GTPase function of the RocCOR domain tandem central to the action of all Roco proteins, and progress in the understanding of its structure and biochemistry is discussed and reviewed. Finally, based on the recent work of our and other labs, a new working hypothesis for the mechanism of Roco proteins is proposed.

scholarly journals High expression levels of the D686N Parkinson's disease mutation in VPS35 induces α-synuclein-dependent toxicity in yeast

2017 ◽  
Vol 16 (1) ◽  
pp. 254-262 ◽  
Author(s):  
Yi Huang ◽  
Xiang Chen ◽  
Xiaofei He ◽  
Caifeng Guo ◽  
Xicui Sun ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
High Expression ◽  
Expression Levels ◽  
Disease Mutation

Neuroprotective Effects of a GLP-2 Analogue in the MPTP Parkinson’s Disease Mouse Model

2021 ◽  
pp. 1-15
Author(s):  
Zijuan Zhang ◽  
Li Hao ◽  
Ming Shi ◽  
Ziyang Yu ◽  
Simai Shao ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Mouse Model ◽  
Neurodegenerative Disorder ◽  
Enzyme Linked Immunosorbent Assay ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Expression Levels ◽  
Dual Agonist

Background: Glucagon-like peptide 2 (GLP-2) is a peptide hormone derived from the proglucagon gene expressed in the intestines, pancreas and brain. Some previous studies showed that GLP-2 improved aging and Alzheimer’s disease related memory impairments. Parkinson’s disease (PD) is a progressive neurodegenerative disorder, and to date, there is no particular medicine reversed PD symptoms effectively. Objective: The aim of this study was to evaluate neuroprotective effects of a GLP-2 analogue in the 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) PD mouse model. Methods: In the present study, the protease resistant Gly(2)-GLP-2 (50 nmol/kg ip.) analogue has been tested for 14 days by behavioral assessment, transmission electron microscope, immunofluorescence histochemistry, enzyme-linked immunosorbent assay and western blot in an acute PD mouse model induced by MPTP. For comparison, the incretin receptor dual agonist DA5-CH was tested in a separate group. Results: The GLP-2 analogue treatment improved the locomotor and exploratory activity of mice, and improved bradykinesia and movement imbalance of mice. Gly(2)-GLP-2 treatment also protected dopaminergic neurons and restored tyrosine hydroxylase expression levels in the substantia nigra. Gly(2)-GLP-2 furthermore reduced the inflammation response as seen in lower microglia activation, and decreased NLRP3 and interleukin-1β pro-inflammatory cytokine expression levels. In addition, the GLP-2 analogue improved MPTP-induced mitochondrial dysfunction in the substantia nigra. The protective effects were comparable to those of the dual agonist DA5-CH. Conclusion: The present results demonstrate that Gly(2)-GLP-2 can attenuate NLRP3 inflammasome-mediated inflammation and mitochondrial damage in the substantia nigra induced by MPTP, and Gly(2)-GLP-2 shows neuroprotective effects in this PD animal model.

scholarly journals Bioinformatics study on genes related to a high-risk postoperative recurrence of lung adenocarcinoma

2021 ◽  
Vol 104 (3) ◽  
pp. 003685042110180
Author(s):  
Xiao Lin ◽  
Meng Zhou ◽  
Zehong Xu ◽  
Yusheng Chen ◽  
Fan Lin
Keyword(s):  
Cell Cycle ◽  
Gene Ontology ◽  
High Risk ◽  
Lung Adenocarcinoma ◽  
Candidate Genes ◽  
Postoperative Recurrence ◽  
High Expression ◽  
Ppi Network ◽  
Hub Genes ◽  
Expression Levels

In this study, we aimed to screen out genes associated with a high risk of postoperative recurrence of lung adenocarcinoma and investigate the possible mechanisms of the involvement of these genes in the recurrence of lung adenocarcinoma. We identify Hub genes and verify the expression levels and prognostic roles of these genes. Datasets of GSE40791, GSE31210, and GSE30219 were obtained from the Gene Expression Omnibus database. Enrichment analysis of gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed for the screened candidate genes using the DAVID database. Then, we performed protein–protein interaction (PPI) network analysis through the database STRING. Hub genes were screened out using Cytoscape software, and their expression levels were determined by the GEPIA database. Finally, we assessed the relationships of Hub genes expression levels and the time of survival. Forty-five candidate genes related to a high-risk of lung adenocarcinoma recurrence were screened out. Gene ontology analysis showed that these genes were enriched in the mitotic spindle assembly checkpoint, mitotic sister chromosome segregation, G2/M-phase transition of the mitotic cell cycle, and ATP binding, etc. KEGG analysis showed that these genes were involved predominantly in the cell cycle, p53 signaling pathway, and oocyte meiosis. We screened out the top ten Hub genes related to high expression of lung adenocarcinoma from the PPI network. The high expression levels of eight genes (TOP2A, HMMR, MELK, MAD2L1, BUB1B, BUB1, RRM2, and CCNA2) were related to short recurrence-free survival and they can be used as biomarkers for high risk of lung adenocarcinoma recurrence. This study screened out eight genes associated with a high risk of lung adenocarcinoma recurrence, which might provide novel insights into researching the recurrence mechanisms of lung adenocarcinoma as well as into the selection of targets in the treatment of the disease.

scholarly journals High expression levels of egfl7 correlate with low endothelial cell activation in peritumoral vessels of human breast cancer

2016 ◽  
Vol 12 (2) ◽  
pp. 1422-1428 ◽  
Author(s):  
Diane Pannier ◽  
Géraldine Philippin-Lauridant ◽  
Marie-Christine Baranzelli ◽  
Delphine Bertin ◽  
Emilie Bogart ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endothelial Cell ◽  
Human Breast Cancer ◽  
Cell Activation ◽  
High Expression ◽  
Human Breast ◽  
Endothelial Cell Activation ◽  
Expression Levels ◽  
Peritumoral Vessels
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