A5090762332- Amyotrophic Lateral Sclerosis Research
- Parkinson's Disease Mechanisms and Treatments
- Neurogenetic and Muscular Disorders Research
- Esophageal and GI Pathology
- Alzheimer's disease research and treatments
- Lysosomal Storage Disorders Research
- Metastasis and carcinoma case studies
- Esophageal Cancer Research and Treatment
- Cholinesterase and Neurodegenerative Diseases
- Nerve injury and regeneration
- Gallbladder and Bile Duct Disorders
- Neuroscience and Neuropharmacology Research
- Pediatric Hepatobiliary Diseases and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Gastric Cancer Management and Outcomes
- Neurological disorders and treatments
- Colorectal Cancer Surgical Treatments
- Gastrointestinal Tumor Research and Treatment
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Muscle Physiology and Disorders
- Hernia repair and management
- Neuroendocrine Tumor Research Advances
- Helicobacter pylori-related gastroenterology studies
- Lung Cancer Research Studies
- Histone Deacetylase Inhibitors Research
Faculdade de Medicina do ABC
2006-2022
Inserm
2010-2022
Université de Strasbourg
2010-2022
Mécanismes Centraux et Périphériques de la Neurodégénérescence
2011-2022
Hospital Estadual Mário Covas
2007-2022
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
2021
Expedeon (Germany)
2010
Hospital la Serena
2010
University of Münster
2008
Max Planck Institute of Experimental Medicine
2008
Bambuterol is a long-acting anti-asthmatic prodrug which releases terbutaline. Terbutaline an agonist of the β2-adrenergic receptors formed by decarbamoylation bambuterol butyrylcholinesterase. Inhibition latter, as well activation β2-AR, are interest for treatment Alzheimer's disease (AD). Combining these two activities, could express good clinical efficacy against AD. The present work firstly confirmed capacity to display in cellulo neuroprotective reduction Tau hyperphosphorylation and...
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that results in progressive loss of motoneurons, motor weakness and death within 1-5 years after onset. Therapeutic options remain limited despite substantial number approaches have been tested clinically. In particular, various neurotrophic factors investigated. Failure these trials has largely ascribed to problems insufficient dosing or inability cross the blood-brain barrier (BBB). We recently uncovered...
Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset disease characterized by upper and lower motor neuron degeneration, muscle wasting paralysis. Growing evidence suggests link between changes in lipid metabolism ALS. Here, we used UPLC/TOF-MS to survey the lipidome SOD1(G86R) mice, model of Significant expression were evident spinal cord skeletal before overt neuropathology. In silico analysis also revealed appreciable sphingolipids including ceramides glucosylceramides (GlcCer)....
Most of the Parkinson's disease (PD) cases are sporadic, although several genes directly related to PD. Several pathways central in PD pathogenesis: protein aggregation linked proteasomal impairments, mitochondrial dysfunctions and impairment dopamine (DA) release. Here we studied close crossing dysfunction α-synuclein (α-syn) extension dopaminergic neuronal death. Here, using rat primary cultures mesencephalic neurons, induced impairments "DA-toxins" (MPP+, 6OHDA, rotenone). We showed that...
Lipid metabolism is drastically dysregulated in amyotrophic lateral sclerosis and impacts prognosis of patients. Animal models recapitulate alterations the energy metabolism, including hypermetabolism severe loss adipose tissue. To gain insight into molecular mechanisms underlying disease progression sclerosis, we have performed RNA-sequencing lipidomic profiling spinal cord symptomatic SOD1G86R mice. Spinal transcriptome mice was characterized by differential expression genes related to...
Spasticity is a common and disabling symptom observed in patients with central nervous system diseases, including amyotrophic lateral sclerosis, disease affecting both upper lower motor neurons. In spasticity traditionally thought to be the result of degeneration neurons cerebral cortex, although other neuronal types, particular serotonergic neurons, might also represent cause spasticity. We performed pathology study seven sclerosis six control subjects that suffer from degenerative process...
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motoneurons. We have recently uncovered new neurotrophic growth factor, granulocyte-colony stimulating factor (G-CSF), which protects α-motoneurons, improves functional outcome, and increases life expectancy SOD-1 (G93A) mice when delivered subcutaneously. However, chronic systemic delivery G-CSF complicated elevation neutrophilic granulocytes. Here, we used adeno-associated virus...
Abstract Recent metabolomic reports connect dysregulation of glycosphingolipids, particularly ceramide and glucosylceramide, to neurodegeneration motor unit dismantling in amyotrophic lateral sclerosis at late disease stage. We report here altered levels gangliosides the cerebrospinal fluid patients early Conduritol B epoxide is an inhibitor acid beta-glucosidase, lowers glucosylceramide degradation. Glucosylceramide precursor for all more complex glycosphingolipids. In SOD1 G86R mice,...
Amyotrophic lateral sclerosis (ALS) is a multifactorial and fatal neurodegenerative disease. Growing evidence connects sphingolipid metabolism to the pathophysiology of ALS. In particular, levels ceramides, glucosylceramides, gangliosides are dysregulated in central nervous system at neuromuscular junctions both animal models patients. Glucosylceramide main precursor complex glycosphingolipids that degraded by lysosomal (GBA1) or non-lysosomal (GBA2) glucocerebrosidase. Here, we report GBA2,...
Amyotrophic Lateral Sclerosis (ALS) is a fatal motoneuron disease, characterized by progressive weakness, muscle wasting and death ensuing 3-5 years after diagnosis. The etiology of ALS complex therapeutic approaches rely mostly on transgenic animal models with SOD-1 mutations. Most frequently employed mouse line for (SOD-1 Tg) that contains point mutation at amino acid position 93 (G->A), present in patients suffering from familial form amyotrophic lateral sclerosis. Here we report (G93A)...
Growing evidence supports a link between fatty acid metabolism and amyotrophic lateral sclerosis (ALS). Here we determined the composition of blood lipids to identify markers disease progression survival. We enrolled 117 patients from two clinical centers 48 these were age gender matched with healthy volunteers. extracted total serum cells, separated methyl esters by gas chromatography. measured circulating biochemical parameters indicative metabolic status. Association readouts was studied,...
Mitochondria, α-syn fibrils and the endo-lysosomal system are key players in pathophysiology of Parkinson’s disease. The toxicity is amplified by cell-to-cell transmission aggregation endogenous species newly invaded neurons. Toxicity PFF was investigated using primary cultures dopaminergic neurons or on aged mice after infusion SNpc combined with mild inhibition GBA. In neurons, application induced a progressive cytotoxicity associated mitochondrial dysfunction, oxidative stress,...
The progressive deterioration of the neuromuscular axis is typically observed in degenerative conditions lower motor neurons, such as amyotrophic lateral sclerosis (ALS). Neurodegeneration this disease associated with systemic metabolic perturbations, including hypermetabolism and dyslipidemia. Our previous gene profiling studies on ALS muscle revealed down-regulation delta-9 desaturase, or SCD1, which rate-limiting enzyme synthesis monounsaturated fatty acids. Interestingly, knocking out...
Cerebral dopamine neurotrophic factor (CDNF) is an unconventional neurotropic that modulates unfolded protein response (UPR) pathway signaling and alleviates endoplasmic reticulum (ER) stress providing cytoprotective effects in different models of neurodegenerative disorders. Here, we developed a brain-penetrating peptidomimetic compound based on human CDNF. This called HER-096 shows similar potency mechanism action as CDNF, promotes neuron survival, reduces α-synuclein aggregation UPR vitro...
Granulocyte colony stimulating factor (G-CSF) is a growth essential for generation of neutrophilic granulocytes. Apart from this hematopoietic function, we have recently uncovered potent neuroprotective and regenerative properties G-CSF in the central nervous system (CNS). The receptor itself are expressed alpha motoneurons, protects improves outcome SOD1(G93A) transgenic mouse model amyotrophic lateral sclerosis (ALS). In vitro, acts anti-apoptotically on motoneuronal cells. Due to...
Mutations in components of the molecular motor dynein/dynactin lead to neurodegenerative diseases system or atypical parkinsonism. These mutations are associated with prominent accumulation vesicles involved autophagy and lysosomal pathways, protein inclusions. Whether alleviating these defects would affect symptoms remain unknown. Here, we show that a mouse model expressing low levels disease linked-G59S mutant dynactin p150Glued develops dysfunction >8 months before loss neurons...
ABSTRACT Bioenergetic deficits, such as mitochondrial impairments and dysfunction in glucose metabolism, have been identified significant contributors to neurodegenerative diseases. Nevertheless, identifying safe effective means address intracellular bioenergetic deficits remains a challenge. This work provides mechanistic insights into the metabolism-regulating function of suspension gold (Au) nanocrystals, referred CNM-Au8®, that are synthesized electrochemically absence any...
Abstract Bioenergetic deficits are known to be significant contributors neurodegenerative diseases. Nevertheless, identifying safe and effective means address intracellular bioenergetic remains a challenge. This work provides mechanistic insights into the energy metabolism‐regulating function of colloidal Au nanocrystals, referred as CNM‐Au8, that synthesized electrochemically in absence surface‐capping organic ligands. When neurons subjected excitotoxic stressors or toxic peptides,...
Introduction: Several generic low-molecular-weight heparins (LMWHs) have recently become available worldwide, including the United States. Companies filed for regulatory approval of versions in many countries, based only on compound biochemical characteristics or its immunogenicity. Methods: Prospective study to evaluate comparative effect 2 enoxaparins (Sanofi-Aventis branded enoxaparin [SAe] vs eurofarma-enoxaparin [Ee], a version) as prophylaxis venous thromboembolism (VTE) following...