Article
Neurosciences
Catherine Bechade, Ivana D'Andrea, Fanny Etienne, Franck Verdonk, Imane Moutkine, Sophie M. Banas, Marta Kolodziejczak, Silvina L. Diaz, Christopher N. Parkhurst, Wenbiao B. Gan, Luc Maroteaux, Anne Roumier
Summary: Severe peripheral infections can induce neuroinflammation and increase the risk of psychiatric disorders, with research highlighting the important role of the 5-HT2B receptor in microglial cells in regulating neuroinflammation.
Article
Pharmacology & Pharmacy
Triana Espinosa-Jimenez, Oriol Busquets, Amanda Cano, Elena Sanchez-Lopez, Ester Verdaguer, Antoni Parcerisas, Jordi Olloquequi, Carme Auladell, Jaume Folch, Walter Wahli, Manuel Vazquez-Carrera, Antoni Camins, Miren Ettcheto
Summary: Peroxisome proliferator-activated receptor beta/delta (PPAR beta/delta) plays a key role in microglial homeostasis and metabolism in the central nervous system. However, its contribution to neuronal and memory processes is still not well-understood. This study aimed to evaluate the role of PPAR beta/delta in neuropathological pathways associated with memory impairment and the modulation of these pathways by obesity. The results showed that PPAR beta/delta deficiency affects neuronal and synaptic structure, leading to memory dysfunction.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Environmental Sciences
Chuan-Hai Li, Dong-Hui Zhang, Li-Dan Jiang, Yuan Qi, Liang-Hong Guo
Summary: This study found that bisphenol analogues could bind to PPAR beta/delta directly, showing transcriptional activity and promoting the expression of target genes. Molecular docking simulation suggested the binding potency and transcriptional activity of bisphenol analogues may depend on their chemical properties. Overall, TBBPA and TCBPA might exert stronger metabolic disruption effects than BPA through the PPAR beta/delta pathway.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2021)
Article
Biochemical Research Methods
Aaron M. Bender, Michael S. Valentine, Joshua A. Bauer, Emily Days, Craig W. Lindsley, W. David Merryman
Summary: A high-throughput screen campaign led to the discovery of highly potent and selective 5-HT2B antagonists. Selected compounds were also evaluated for their ability to cross the blood-brain barrier. Two compounds, VU0530244 and VU0631019, showed limited potential for brain penetration, making them promising candidates for the development of 5-HT2B antagonists without centrally-mediated adverse effects.
ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES
(2023)
Article
Chemistry, Organic
Francisco J. Fuentes-Pantoja, Alejandro Cordero-Vargas
Summary: The new synthesis approach, based on photoredox catalysis, can be used to synthesize various natural products containing α,β-unsaturated δ-lactones.
SYNTHESIS-STUTTGART
(2021)
Review
Pharmacology & Pharmacy
Takayuki Koga, Jeffrey M. Peters
Summary: Excessive and chronic alcohol consumption can lead to alcoholic liver disease, which is influenced by multiple factors and may be modulated by PPARs. PPAR beta/delta could potentially be targeted for the treatment and prevention of alcoholic liver disease, although its role requires further clarification.
BIOLOGICAL & PHARMACEUTICAL BULLETIN
(2021)
Review
Neurosciences
Anna K. Strosznajder, Sylwia Wojtowicz, Mieszko J. Jezyna, Grace Y. Sun, Joanna B. Strosznajder
Summary: PPAR-beta/delta is a nuclear receptor involved in lipid metabolism and cellular functions, playing a potential role in inflammation and disease treatment. Its role in neurodegeneration and neuroinflammation remains poorly understood, despite potential therapeutic applications in neurological disorders.
NEUROMOLECULAR MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Caroline Caetano da Silva, Thomas Edouard, Melanie Fradin, Marion Aubert-Mucca, Manon Ricquebourg, Ratish Raman, Jean Pierre Salles, Valerie Charon, Pascal Guggenbuhl, Marc Muller, Martine Cohen-Solal, Corinne Collet
Summary: This study identifies WNT11 as a novel gene responsible for early onset osteoporosis. Loss-of-function variants of WNT11 inhibit bone formation through the Wnt canonical and non-canonical pathways. WNT11 activates Wnt signaling by inducing the RSPO2-LGR5 complex via the non-canonical Wnt pathway.
HUMAN MOLECULAR GENETICS
(2022)
Article
Cardiac & Cardiovascular Systems
Olivier Schussler, Luc Maroteaux, Ramadan Jashari, Pierre Falcoz, Marco Alifano, Yves Lecarpentier, Jean-Marie Launay
Summary: This study quantitatively measured the expression of 5-HTR serotonin receptors on animal or human valvular tissues, identifying several new and robustly expressed proteins and observing correlations between different levels of 5-HTR expression. These findings provide insights into the signaling mechanisms involved in valvular fibrosis and degeneration.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Endocrinology & Metabolism
Martine Cohen-Solal, Corinne Collet, Pascal Bizot, Cecile Pavis, Thomas Funck-Brentano
Summary: Osteopetrosis is characterized by high bone mineral density due to osteoclast failure. Major complications in adults include delayed fracture healing, vision and hearing loss, spleen enlargement, and marrow failure. Multidisciplinary teams, patient organizations, and patient-reported outcomes are essential for managing the disease and its complications. A questionnaire survey revealed patient concerns about anxiety, disability, disease transmission, insufficient clinician training, and fear of inappropriate fracture management. Effective training and improved awareness by healthcare professionals and policymakers can reduce the burden of osteopetrosis.
Article
Endocrinology & Metabolism
Gretl Hendrickx, Eveline Boudin, Ellen Steenackers, Corinne Collet, Geert R. Mortier, David Genevi, Wim Van Hul
Summary: CDD is a rare and severe bone dysplasia characterized by progressive sclerosis of the cranial and facial bones. In this study, two individuals from a consanguineous family with mild phenotypic features of CDD were investigated. Serum analysis revealed high levels of bone turnover markers, and exome sequencing identified a homozygous missense variant in the SP7 gene. Further studies are needed to understand the underlying mechanisms of how SP7 variants cause sclerosing bone dysplasia.
Article
Biochemistry & Molecular Biology
Federico Di Rocco, Massimiliano Rossi, Isabelle Verlut, Alexandru Szathmari, Pierre Aurelien Beuriat, Nicolas Chatron, Julie Chauvel-Picard, Carmine Mottolese, Pauline Monin, Matthieu Vinchon, Sofia Guernouche, Corinne Collet
Summary: In infants with isolated single-suture synostosis, underlying genetic variants can be found. In this study, we investigated the molecular basis of isolated sagittal and metopic craniosynostosis in infants who had undergone surgery at a national reference center. Among 101 infants, 13 carried variants in genes associated with craniosynostosis. SMAD6 variants were the most common, and children with these variants showed delayed language acquisition. Our findings emphasize the importance of molecular analysis in understanding the pathophysiology of midline craniosynostosis.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Genetics & Heredity
Adrien Bloch, Guillaume Couture, Bertrand Isidor, Manon Ricquebourg, Emmanuelle Bourrat, Dan Lipsker, Bruno Taillan, Alice Combier, Christine Chiaverini, Frederique Moufle, Bruno Delobel, Pascal Richette, Corinne Collet
Summary: Primary hypertrophic osteoarthropathy (PHO), also known as pachydermoperiostosis, is characterized by digital clubbing, periostosis, and pachydermia. PHO is caused by mutations in the SLCO2A1 and HPGD genes. While traditionally considered an autosomal recessive disorder, recent evidence suggests the existence of an autosomal dominant form of PHO, which was demonstrated for SLCO2A1 for the first time in 2021.
EUROPEAN JOURNAL OF MEDICAL GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Lotte Goyvaerts, Anica Schraenen, Katleen Lemaire, Peter in't Veld, Ilse Smolders, Luc Maroteaux, Frans Schuit
Summary: Islet serotonin and 5-HT2B receptors are not necessary for beta cell proliferation during normal mouse pregnancy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Christelle Nilles, Mickael Alexandre Obadia, Rodolphe Sobesky, Jerome Dumortier, Olivier Guillaud, Chloe Laurencin, Caroline Moreau, Claire Vanlemmens, Fabienne Ory-Magne, Victor de Ledinghen, Edouard Bardou-Jacquet, Frederique Fluchere, Corinne Collet, Nouzha Oussedik-Djebrani, France Woimant, Aurelia Poujois
Summary: This study characterized the clinical presentation, therapeutic management, and outcomes of late-onset Wilson's disease (WD). Late-onset WD mainly presented with neurological symptoms, and 30% of neurological symptoms were atypical. Personalized treatment improved prognosis, highlighting the importance of considering WD at any age and in cases of atypical presentation.
MOVEMENT DISORDERS
(2023)
Article
Biochemistry & Molecular Biology
Giulia Albertini, Ivana D'Andrea, Melanie Druart, Catherine Bechade, Nayadoleni Nieves-Rivera, Fanny Etienne, Corentin Le Magueresse, Alexandra Rebsam, Nicolas Heck, Luc Maroteaux, Anne Roumier
Summary: The proper maturation of emotional and sensory circuits in early postnatal development is dependent on the fine-tuning of serotonin (5-HT) levels. Dysfunctions of the serotonergic system have been associated with neurodevelopmental psychiatric diseases, including autism spectrum disorders (ASD). This study focused on the role of microglia, which play a role in brain wiring refinement, and investigated how the control of these cells by 5-HT affects neurodevelopment and spontaneous behaviors in mice. The results showed that impairing the serotonergic control of microglia during early postnatal development affects the phagolysosomal compartment of these cells, perturbs neuronal circuits maturation, and leads to adult hyperactivity and behavioral defects in sociability and flexibility.
MOLECULAR PSYCHIATRY
(2023)
Review
Developmental Biology
Caroline Caetano da Silva, Agnes Ostertag, Ratish Raman, Marc Muller, Martine Cohen-Solal, Corinne Collet
Summary: Wnt signaling plays a crucial role in osteoblast differentiation and mineralization through canonical and noncanonical pathways. The zebrafish silberblick mutant with a wnt11f2 mutation shows defects in embryonic morphogenesis, and this review aims to summarize its characterization and role in skeletal development. In addition to early developmental defects and craniofacial dysmorphia, the heterozygous mutant also exhibits increased tissue mineral density, suggesting a potential role of wnt11f2 in high bone mass phenotypes.
Article
Endocrinology & Metabolism
Stephanie Fabre, Morgane Bourmaud, Guillaume Mabilleau, Ruben Goulet, Aude Couturier, Alexandre Dentel, Serge Picaud, Thomas Funck-Brentano, Corinne Collet, Martine Cohen-Solal
Summary: This study found that the V667M variant of the LRP5 gene is associated with low bone mineral density and osteoporosis, as well as eye abnormalities. Patients and mice with this variant showed low bone density, altered bone microarchitecture, and impaired bone matrix quality. Additionally, retinal vascular abnormalities were observed in the mouse model.
Article
Multidisciplinary Sciences
Amina Benhadda, Celia Delhaye, Imane Moutkine, Xavier Marques, Marion Russeau, Corentin Le Magueresse, Anne Roumier, Sabine Levi, Luc Maroteaux
Summary: Many psychiatric diseases are associated with dysfunction of serotonin (5-HT) neurons. This study shows that 5-HT1A and 5-HT2B receptors can form heterodimers and co-cluster at the plasma membrane of dendrites. Stimulation of these receptors prevents 5-HT1A receptor internalization and increases 5-HT2B receptor membrane clustering, regulating the excitability of serotonergic neurons.
Article
Immunology
Maxence Cornille, Stephanie Moriceau, Roman H. Khonsari, Yann Heuze, Lea Loisay, Valerie Boitez, Anne Morice, Eric Arnaud, Corinne Collet, Morad Bensidhoum, Nabil Kaci, Nathalie Boddaert, Giovanna Paternoster, Theresa Rauschendorfer, Sabine Werner, Suzanne L. Mansour, Federico Di Rocco, Franck Oury, Laurence Legeai-Mallet
Summary: A gain-of-function mutation in the FGFR3 gene can lead to learning and memory impairments independent of skull abnormalities. Researchers developed a mouse model of Crouzon syndrome and found that the mice exhibited memory impairments and abnormalities in brain structure and signaling pathways. Modulating the FGFR3 signaling pathway could be valuable for treating neurological disorders associated with craniosynostosis.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Endocrinology & Metabolism
Caroline Ea, Quentin Hennocq, Arnaud Picard, Michel Polak, Corinne Collet, Laurence Legeai-Mallet, Eric Arnaud, Giovanna Paternoster, Roman Hossein Khonsari
Summary: Patients with FGFR-related faciocraniosynostoses exhibit clinically significant extra-cranial anomalies, and two specific age periods (1-3 years and >8 years) are associated with lower height and weight values. Growth hormone treatment did not fully restore normal growth in height and weight for these patients.
Article
Endocrinology & Metabolism
Coline Rouleau, Margaux Malorie, Corinne Collet, Valerie Porquet-Bordes, Isabelle Gennero, Sanaa Eddiry, Michel Laroche, Jean Pierre Salles, Guillaume Couture, Thomas Edouard
Summary: This study described the clinical and bone characteristics in a large cohort of children and young adults with idiopathic primary osteoporosis, and highlighted the importance of identifying genetic variants through genomic sequencing in these patients.