Transcriptional profile of Parkinson blood mononuclear cells with LRRK2 mutation

Mutez, Eugénie; Larvor, Lydie; Leprêtre, Frédéric; Mouroux, Vincent; Hamalek, D.; Kerckaert, Jean‐Pierre; Pérez-Tur, Jordi; Waucquier, N.; Vanbesien-Mailliot, Christel; Duflot, Aurélie; Devos, David; Defebvre, Luc; Kreisler, Alexandre; Frigard, B.; Destée, Alain; Chartier-Harlin, Marie-Christine

doi:10.1016/j.neurobiolaging.2009.10.016

Cited by 82 publications

(81 citation statements)

References 45 publications

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“…Two experiments are particularly interesting because they used leukocytes from PD patients with the G2019S mutation (99,100). One study performed protein array analysis to compare MAPK activity between patients and healthy controls and reported that phosphorylation of Src, c-JNK and heat shock protein 27 (HSP27) in patients' samples are lower than in the controls (99).…”

Section: Normal and Pathological Features Of Lrrk2mentioning

confidence: 99%

“…Mutez et al carried out a microarray experiment using peripheral blood mononuclear cells of PD patients with the G2019S mutation. Their analysis detected differentially expressed genes common to the PD patients in comparison with the healthy controls, and ontology analysis of the genes revealed perturbation of pathways related to PD-related neurodegeneration, such as ubiquitin-regulated protein degradation, mitochondrial oxidation, axonal guidance, inflammation and apoptosis (100). Metabolomic analysis was also applied to plasma samples from PD patients with or without the LRRK2 G2019S mutation, along with healthy controls (101).…”

Section: Normal and Pathological Features Of Lrrk2mentioning

confidence: 99%

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Biochemical and molecular features of LRRK2 and its pathophysiological roles in Parkinson's disease

Seol

2010

BMB Reports

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Parkinson's disease (PD) is the second most common neurodegenerative disease, and 5-10% of the PD cases are genetically inherited as familial PD (FPD). LRRK2 (leucine-rich repeat kinase 2) was first reported in 2004 as a gene corresponding to PARK8, an autosomal gene whose dominant mutations cause familial PD. LRRK2 contains both active kinase and GTPase domains as well as protein-protein interaction motifs such as LRR (leucine-rich repeat) and WD40. Most pathogenic LRRK2 mutations are located in either the GTPase or kinase domain, implying important roles for the enzymatic activities in PD pathogenic mechanisms. In comparison to other PD causative genes such as parkin and PINK1, LRRK2 exhibits two important features. One is that LRRK2's mutations (especially the G2019S mutation) were observed in sporadic as well as familial PD patients. Another is that, among the various PDcausing genes, pathological characteristics observed in patients carrying LRRK2 mutations are the most similar to patients with sporadic PD. Because of these two observations, LRRK2 has been intensively investigated for its pathogenic mechanism (s) and as a target gene for PD therapeutics. In this review, the general biochemical and molecular features of LRRK2, the recent results of LRRK2 studies and LRRK2's therapeutic potential as a PD target gene will be discussed. [BMB reports 2010; 43(4): 233-244]

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Section: Normal and Pathological Features Of Lrrk2mentioning

confidence: 99%

Section: Normal and Pathological Features Of Lrrk2mentioning

confidence: 99%

Biochemical and molecular features of LRRK2 and its pathophysiological roles in Parkinson's disease

Seol

2010

BMB Reports

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“…The miRNA and mRNA expression profiles of PD were downloaded from the Gene Expression Omnibus and were termed GSE16658 (http://www.ncbi.nlm.nih.gov/geo/quer y/ acc.cgi?acc=GSE16658; accessed 9th June 2013) and GSE22491 (http://www.ncbi.nlm.nih.gov/geo/query/acc. cgi?acc=GSE22491; accessed 9th June 2013), respectively (13,14). miRNA expression profiling was performed using the miRCURY LNA microRNA Array platform, which included 32 samples (19 PD samples and 13 normal control samples).…”

Section: Methodsmentioning

confidence: 99%

Bioinformatic analysis of microRNA expression in Parkinson’s disease

Hao

Chen

Dai

et al. 2014

Molecular Medicine Reports

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Abstract. Parkinson's disease (PD) is a type of movement disorder caused by loss of dopamine-producing neurons in the midbrain. In order to identify the synergistic microRNA (miRNA) pattern in PD, miRNA and mRNA double expression profiles of PD were downloaded. Differentially expressed miRNA and mRNA were identified [P<0.01, following false discovery rate (FDR) correction]. A cumulative hypergeometric distribution test was then performed to identify synergistic miRNAs (P<0.01, following FDR correction). Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotations were performed to analyze the miRNA regulatory target genes. Subsequently, a synergistic miRNA network was constructed and miRNAs exhibiting a high degree were identified. In total, 200 differentially expressed miRNA and 2,966 differentially expressed mRNA were identified. In addition, 1,502 synergistic miRNA interactions were identified, and miRNAs regulated 304 target genes in total. The GO and KEGG analysis demonstrated that these target genes were enriched in biosynthetic and cellular biosynthetic processes, the assembly of cellular components in morphogenesis, mitogen-activated protein kinase signaling, myometrial relaxation and contraction pathways as well as calcium regulation. The miRNA network demonstrated that miR-627, miR-634, miR-514, miR-563 and miR-613 had a high degree. miRNA with a high degree may be associated with the pathogenesis of PD and, therefore, may assist in the diagnosis and therapy of PD.

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“…Similarly, actin is transported at a slow rate to the neurofilament by molecular motors, constituting, along with other proteins, slow component b. Recent studies have revealed that impairment of actin axonal transport has been reported in a number of neurodegenerative diseases such as spinal muscle atrophy 56 , Alzheimer's 57,58 , Parkinson's-related α-synucleinopathy 59 or diabetic neuropathy 15 . Mechanisms underlying the impairment of actin axonal transport are not clearly established but, as in the case of neurofilament, it is speculated that structural and/ or functional changes in molecular motor and cytoskeleton-associated proteins are causative of the observed impairment.…”

Section: Actinmentioning

confidence: 99%

Axonal transport of cytoskeleton and cytoskeleton regulatory cargo proteins in neurodegenerative disorders

Juranek¹

2013

OA Anatomy

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Transcriptional profile of Parkinson blood mononuclear cells with LRRK2 mutation

Cited by 82 publications

References 45 publications

Biochemical and molecular features of LRRK2 and its pathophysiological roles in Parkinson's disease

Biochemical and molecular features of LRRK2 and its pathophysiological roles in Parkinson's disease

Bioinformatic analysis of microRNA expression in Parkinson’s disease

Axonal transport of cytoskeleton and cytoskeleton regulatory cargo proteins in neurodegenerative disorders

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