A5025413909- Parkinson's Disease Mechanisms and Treatments
- Genetic Neurodegenerative Diseases
- Metabolism and Genetic Disorders
- RNA regulation and disease
- RNA Research and Splicing
- Neuroscience and Neuropharmacology Research
- Neurological diseases and metabolism
- Amino Acid Enzymes and Metabolism
- Neurotransmitter Receptor Influence on Behavior
- Nuclear Receptors and Signaling
- Aldose Reductase and Taurine
- Genetics and Neurodevelopmental Disorders
- RNA and protein synthesis mechanisms
- Hypothalamic control of reproductive hormones
- Alzheimer's disease research and treatments
- Reproductive biology and impacts on aquatic species
- Glycogen Storage Diseases and Myoclonus
- Biochemical effects in animals
- Aquaculture disease management and microbiota
- Plant Gene Expression Analysis
- Tryptophan and brain disorders
- Cell death mechanisms and regulation
- Free Radicals and Antioxidants
- Diet and metabolism studies
- Circadian rhythm and melatonin
Sanofi (France)
2003-2020
Centre National de la Recherche Scientifique
1988-2002
Pitié-Salpêtrière Hospital
2002
Sorbonne Université
2002
Centre de Génétique Moléculaire
1995
Laboratoire de Neurobiologie Cellulaire et Moléculaire
1988-1991
Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of late-onset, autosomal-dominant familial Parkinson's disease (PD). LRRK2 functions as both a and GTPase, PD-linked mutations known to influence enzymatic activities. While can commonly induce neuronal damage culture models, mechanisms underlying these pathogenic effects remain uncertain. Rodent models containing often lack robust PD-like neurodegenerative phenotypes. Here, we develop preclinical model PD adult rats...
The human gene for tryptophan hydroxylase has been previously assigned to chromosome 11 by analysis of a panel somatic cell hybrids. We report here on the refinement this localization in situ hybridization.
Journal Article Complete coding sequence of human tryptophan hydroxylase Get access Sylviane Boularand, Boularand Search for other works by this author on: Oxford Academic PubMed Google Scholar Michèle C. Darmon, Darmon Yves Ganem, Ganem 1Servicesde Biochimie et Neuroendocrinologie, Hôpital Saint-Louis75475 Paris Cedex 10, France Jean-Marie Launay, Launay Jacques Mallet * To whom correspondence should be addressed Nucleic Acids Research, Volume 18, Issue 14, 25 July 1990, Page 4257,...
A single human gene has been described to encode multiple tyrosine hydroxylase (TH) mRNAs. The study of this variation extended by S1 mapping experiments and analysis the 5' region TH gene. Four different mRNAs were found originate solely from alternative splicing two exons. Comparison flanking regions rat genes discloses several highly conserved segments, likely play an important role in regulation expression.
Abstract Leucine-rich repeat kinase 2 (LRRK2) is a promising therapeutic target for the treatment of Parkinson’s disease (PD) and LRRK2 inhibitors are currently being tested in early phase clinical trials. In order to ensure highest chance success, biomarker-guided entry into trials key. phosphorylation, phosphorylation substrate Rab10, have been proposed as engagement biomarkers inhibition. However, pharmacodynamic biomarker demonstrate that biological response has occurred lacking. We...
We isolated and sequenced 2,117 nucleotides of the promoter region human tryptophan hydroxylase (TPH) gene. Transient transfection in pinealocyte cultures PC12 cells was used to investigate TPH (hTPH) gene activity its regulation by cAMP signaling pathway. A base pairs upstream transcription initiation site hTPH efficiently directed a luciferase reporter but not cell-specific manner. The significantly enhanced cyclic AMP analog two cell types. Deletion analysis showed that from −73 +2 is...
We report the isolation and organization of gene encoding human tryptophan hydroxylase (TPH) an analysis corresponding mRNAs. The spans a region 29 kilobases, which contains at least 11 exons variably spliced 5′-untranslated (5′-UTR). sequence coding majority positions intron-exon boundaries TPH are very similar to those tyrosine phenylalanine hydroxylase, other members aromatic amino acid family. Phylogenetic evidences early divergence independent evolution three types. cDNA cloning...
Abstract Two clones encoding human glial fibrillary acidic protein (GFAP) were isolated from a astrocytoma cDNA library. The pHGFAP1 and pHGFAP2 selected by the combined use of differential colony hybridization hybridization‐selection technique with polyclonal anti GFAP antiserum. longer one, pHGFAP1, encompasses 3.0 kb includes 1.8 long 3′ untranslated region specific to mRNA. Sequence data disclosed an extensive homology within coding mouse cDNAs even in end domains. Blot analysis RNAs...
Abstract The expression of the tryptophan hydroxylase (TPH) gene, encoding rate‐limiting enzyme serotonin biosynthesis, is tightly regulated both at transcriptional and post‐transcriptional levels. In pineal gland, transcription gene activated in response to an intracellular circadian increase cAMP concentration. We have previously shown that a 2.1‐kb fragment human TPH promoter induced by cAMP, although it lacks canonical responsive element, CRE. minimal (−73/+29) has only weak activity but...
Abstract: We report the isolation of a full‐length eel tyrosine hydroxylase (TH) cDNA that is characterized by long 3′ untranslated region and diversity restricted to end owing differential use three polyadenylation signals. The longest TH mRNA was distinctive in presence four pentameric elements (AUUUA) AU‐rich noncoding region. Such could provide basis posttranscriptional or translational regulation gene expression. Comparison sequence with those other aromatic amino acid hydroxylases (TH,...
Changes in gene expression within the hippocampus induced by denervation after electrolytic fimbria-fornix lesion rat were compared to morphological and biochemical alterations. Fimbria-fornix results degeneration of hippocampal cholinergic terminals as evidenced a sustained (2 days 1 month) decrease cholineacetyltransferase (ChAT) activity (50%). These changes accompanied growth associated protein 43 (GAP-43) immunoreactivity all layers 4 followed subsequent increase return normal levels 20...
Abstract Several regulatory neurotactors, classically associated with the hypothalamus, may be synthesized in anterior pituitary (AP). Dopamine (DA) is main prolactin‐inhibiting factor. Its de novo synthesis normal AP has not been proved, although TH transcript previously demonstrated by RT/PCR AP. We investigated tyrosine hydroxylase (TH) gene expression at both protein and mRNA levels of random cycling female rats a catecholaminergic tissue, adrenal gland (AG). The Western blot analysis...
A bstract Mutations in the leucine-rich repeat kinase 2 ( LRRK2 ) gene cause late-onset, autosomal dominant familial Parkinson’s disease (PD) and represent most common known of PD. can function as both a protein GTPase PD-linked mutations are to influence these enzymatic activities. While commonly induce neuronal damage toxicity cellular models, mechanisms underlying pathogenic effects remain uncertain. Rodent models based upon often lack hallmark features PD robust neurodegenerative...
Abstract Hyper-activated LRRK2 is linked to Parkinson’s disease susceptibility and progression. Quantitative measures of inhibition, especially in the brain, may be critical clinical development successful LRRK2-targeting therapeutics. In this study, three different brain-penetrant selective small-molecule kinase inhibitors (PFE-360, MLi2, RA283) were orally administered groups cynomolgus macaques at doses. Biofluid markers with proposed pharmacodynamic properties for assessing inhibition...
Background: Hyper-activated LRRK2 is linked to Parkinson’s disease susceptibility and progression. Quantitative measures of inhibition, especially in the brain, may be critical development successful LRRK2- targeting therapeutics.Methods: Three structurally distinct, brain-penetrant, selective small-molecule kinase inhibitors (PFE360, MLi2, RA283) were orally administered groups cynomolgus macaques at different doses. Biofluid markers with proposed predictive value for assessing inhibition...