A5037440459- Multiple Sclerosis Research Studies
- Peripheral Neuropathies and Disorders
- Sphingolipid Metabolism and Signaling
- Ion Transport and Channel Regulation
- Renal Diseases and Glomerulopathies
- Cerebrovascular and genetic disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Toxin Mechanisms and Immunotoxins
- Renal and related cancers
- Herpesvirus Infections and Treatments
- Cell Adhesion Molecules Research
- Electrolyte and hormonal disorders
- Genetic and Kidney Cyst Diseases
- T-cell and B-cell Immunology
- Moyamoya disease diagnosis and treatment
- Intracerebral and Subarachnoid Hemorrhage Research
- Neonatal Respiratory Health Research
- Hereditary Neurological Disorders
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Neurological Disease Mechanisms and Treatments
- Myasthenia Gravis and Thymoma
- Alzheimer's disease research and treatments
- Microfluidic and Bio-sensing Technologies
- Lysosomal Storage Disorders Research
- Ion channel regulation and function
Inserm
2008-2020
Université Paris Cité
2008-2020
Institut de Psychiatrie et Neurosciences de Paris
2019-2020
Délégation Paris 7
2015
Sorbonne Paris Cité
2015
University of California, San Francisco
2011-2014
Hôpital Necker-Enfants Malades
2008-2009
Délégation Paris 5
2008-2009
Institut Curie
2008
Institut Pasteur
2008
The astrocyte water channel aquaporin-4 (AQP4) is expressed as heterotetramers of M1 and M23 isoforms in which the presence M23–AQP4 promotes formation large macromolecular aggregates termed orthogonal arrays. Here, we demonstrate that AQP4 aggregation state determines its subcellular localization cellular functions. Individually M1–AQP4 was freely mobile plasma membrane could diffuse into rapidly extending lamellipodial regions to support cell migration. In contrast, formed arrays did not...
Podocin is a critical component of the glomerular slit diaphragm, and genetic mutations lead to both familial sporadic forms steroid-resistant nephrotic syndrome. In mice, constitutive absence podocin leads rapidly progressive renal disease characterized by mesangiolysis and/or mesangial sclerosis Using established Cre-loxP technology, we inactivated in adult mouse kidney podocyte-specific manner. Progressive loss glomerulus recapitulated albuminuria, hypercholesterolemia, hypertension,...
The pathogenesis of neuromyelitis optica (NMO) involves binding IgG autoantibodies (NMO-IgG) to aquaporin-4 (AQP4) on astrocytes in the central nervous system (CNS). We studied vivo processing mice a recombinant monoclonal human NMO-IgG that binds strongly mouse AQP4. Following intravenous administration, serum [NMO-IgG] decreased with t1/2 ∼18 hours wildtype and ∼41 AQP4 knockout mice. was localized AQP4-expressing cell membranes kidney (collecting duct), skeletal muscle, trachea...
Abstract Objective: Neuromyelitis optica (NMO) is caused by binding of pathogenic autoantibodies (NMO‐immunoglobulin G [IgG]) to aquaporin‐4 (AQP4) on astrocytes, which initiates complement‐dependent cytotoxicity (CDC) and inflammation. We recently introduced mutated antibody (aquaporumab) small‐molecule blocker strategies for therapy NMO, based prevention NMO‐IgG AQP4. Here, we investigated an alternative strategy involving neutralization effector function selective IgG heavy‐chain...
Aquaporin-4 (AQP4), the principal water channel in astrocytes, is involved brain movement, inflammation, and neuroexcitation. In this study, there was strong neuroprotection mice lacking AQP4 a model of global cerebral ischemia produced by transient, bilateral carotid artery occlusion (BCAO). Survival neurological outcome were greatly improved AQP4-/- vs. AQP4+/+ after occlusion, with large robust differences both outbred (CD1) inbred (C57bl/6) mouse strains without or mechanical...
Spontaneous deep intracerebral hemorrhage (ICH) is a devastating subtype of stroke without specific treatments. It has been thought that smooth muscle cell (SMC) degeneration at the site arteriolar wall rupture may be sufficient to cause hemorrhage. However, ICHs are rare in some aggressive small vessel diseases characterized by significant SMC degeneration. Here we hypothesized second cellular defect required for occurrence ICH.We studied genetic model spontaneous ICH using Col4a1+/G498V...
Aquaporin-4 (AQP4) is a water channel expressed in astrocytes, skeletal muscle and epithelial cells that forms supramolecular aggregates plasma membranes called orthogonal arrays of particles (OAPs). AQP4 as short isoform (M23) large OAPs, long (M1) does not form OAPs by itself but can mingle with M23 to relatively small OAPs. were imaged ~20 nm spatial precision photoactivation localization microscopy (PALM) expressing chimeras M1- or M23-AQP4 photoactivatable fluorescent proteins. Native...
Although optic neuritis (ON) is a defining feature of neuromyelitis optica (NMO), appropriate animal models NMO ON are lacking. Most patients seropositive for immunoglobulin G autoantibodies (NMO-IgG) against the astrocyte water channel aquaporin-4 (AQP4). Several approaches were tested to develop robust, passive-transfer mouse model ON, including NMO-IgG and complement delivery by: (i) retrobulbar infusion; (ii) intravitreal injection; (iii) single intracranial injection near chiasm; (iv)...
Abstract Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic paradigm of small vessel disease (SVD) caused by NOTCH3 mutations that stereotypically lead to the vascular accumulation around smooth muscle cells pericytes. White matter (WM) lesions (WMLs) are earliest most frequent abnormalities, can be associated lacunar enlarged perivascular spaces (ePVS). The prevailing view blood brain barrier (BBB) leakage, possibly mediated...
Neuromyelitis optica (NMO) is thought to be caused by immunoglobulin G autoantibodies (NMO-IgG) against astrocyte water channel aquaporin-4 (AQP4). A recent study (Hinson et al. (2012) Proc Natl Acad Sci USA 109:1245-1250) reported that NMO-IgG inhibits AQP4 permeability directly and causes rapid cellular internalization of the M1 but not M23 isoform AQP4, resulting in clustering, enhanced complement-dependent cytotoxicity, tissue swelling. Here, we report evidence challenging this proposed...
Objective CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), caused by mutations in the NOTCH3 receptor, is most aggressive small vessel disease of brain. A key feature its pathogenesis accumulation extracellular domain receptor (Notch3 ECD ) vessels, formation characteristic deposits termed granular osmiophilic material (GOM). Here, we investigated therapeutic potential a mouse monoclonal antibody (5E1) that specifically recognizes Notch3 ....
The Wilms tumor-suppressor gene WT1, a key player in renal development, also has crucial role maintenance of the glomerulus mature kidney. However, molecular pathways orchestrated by WT1 podocytes, where it is highly expressed, remain unknown. Their defects are thought to modify cross-talk between podocytes and other glomerular cells ultimately lead sclerosis, as observed diffuse mesangial sclerosis (DMS) nephropathy associated with mutations. To identify podocyte targets, we generated novel...
Abstract Mutations in the α1 (COL4A1) or α2 (COL4A2) chains of collagen type IV, a major component vascular basement membrane, cause intracerebral haemorrhages with variable expressivity and reduced penetrance by mechanisms that remain poorly understood. Here we sought to investigate cellular COL4A1‐related haemorrhage identify marker for risk stratification. A combination histological, immunohistochemical, electron microscopy analyses were used analyse brain parenchyma, cerebrovasculature,...
Neuromyelitis optica (NMO) is characterized by inflammatory demyelinating lesions of the spinal cord and optic nerves from an autoimmune response against water channel aquaporin-4 (AQP4). We report 2 patients with transient hyperCKemia associated NMO suggesting possible skeletal muscle damage.Patient 1 was a 72-year-old man who presented soreness elevated serum creatine kinase (CK) preceding initial attack NMO. Patient 25-year-old woman established diagnosis diffuse myalgias, proximal upper...