A5056258350- Virus-based gene therapy research
- Peroxisome Proliferator-Activated Receptors
- Alzheimer's disease research and treatments
- RNA Interference and Gene Delivery
- RNA regulation and disease
- Lysosomal Storage Disorders Research
- Cholesterol and Lipid Metabolism
- Genetic Neurodegenerative Diseases
- Metabolism and Genetic Disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer, Hypoxia, and Metabolism
- Hormonal Regulation and Hypertension
- Nuclear Receptors and Signaling
- Cytomegalovirus and herpesvirus research
- CRISPR and Genetic Engineering
- Adipose Tissue and Metabolism
- Mitochondrial Function and Pathology
- Diet and metabolism studies
- Polysaccharides and Plant Cell Walls
- Neurogenesis and neuroplasticity mechanisms
- Ubiquitin and proteasome pathways
- Viral Infectious Diseases and Gene Expression in Insects
- Tryptophan and brain disorders
- Cholinesterase and Neurodegenerative Diseases
- Neuroscience and Neuropharmacology Research
Sorbonne Université
2019-2024
Institut du Cerveau
2019-2024
Inserm
2015-2024
Centre National de la Recherche Scientifique
1992-2024
Assistance Publique – Hôpitaux de Paris
2008-2023
Institut de Psychiatrie et Neurosciences de Paris
2023
AskBio (United States)
2023
Université Paris-Saclay
2015-2022
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
2014-2022
Institut Jacques Monod
2021-2022
Slowing Brain Disease with Gene Therapy X-linked adrenoleukodystrophy (ALD), the hereditary brain demyelinating disorder that was featured in movie “ Lorenzo's Oil ,” is typically treated by transplantation of bone marrow from matched donors. This treatment slows progression disease introducing cells differentiate into myelin-producing cells. Cartier et al. (p. 818 ; see Perspective Naldini ) tested an alternative gene therapy–based approach two young patients without A lentiviral vector...
Abnormalities in neuronal cholesterol homeostasis have been suspected or observed several neurodegenerative disorders including Alzheimer's disease, Parkinson's disease and Huntington's disease. However, it has not demonstrated whether an increased abundance of neurons vivo contributes to neurodegeneration. To address this issue, we used RNA interference methodology inhibit the expression 24-hydroxylase, encoded by Cyp46a1 gene, hippocampus normal mice. Cholesterol 24-hydroxylase controls...
Adrenomyeloneuropathy is an X-linked recessive disorder characterized by myelopathy, peripheral neuropathy, and cerebral demyelination, which develop in association with the accumulation of very-long-chain fatty acids. The administration oleic erucic acids inhibits synthesis Recently such dietary treatment has been widely publicized as a possible cure for this disease.
The development of Alzheimer's disease (AD) is closely connected with cholesterol metabolism. Cholesterol increases the production and deposition amyloid-beta (Abeta) peptides that result in formation amyloid plaques, a hallmark pathology. In brain, synthesized situ but cannot be degraded nor cross blood-brain barrier. major exportable form brain 24S-hydroxycholesterol, an oxysterol generated by neuronal 24-hydroxylase encoded CYP46A1 gene. We report injection adeno-associated vector (AAV)...
Interleukin-2 (IL-2)-deficient mice have cytoarchitectural hippocampal modifications and impaired learning memory ability reminiscent of Alzheimer's disease. IL-2 stimulates regulatory T cells whose role is to control inflammation. As neuroinflammation contributes neurodegeneration, we investigated in Therefore, levels biopsies patients with disease relative age-matched individuals. We then treated APP/PS1ΔE9 having established for 5 months using single administration an AAV-IL-2 vector....
Huntington’s disease is an autosomal dominant neurodegenerative caused by abnormal polyglutamine expansion in huntingtin (Exp-HTT) leading to degeneration of striatal neurons. Altered brain cholesterol homeostasis has been implicated disease, with increased accumulation neurons yet reduced levels metabolic precursors. To elucidate these two seemingly opposing dysregulations, we investigated the expression 24-hydroxylase (CYP46A1), neuronal-specific and rate-limiting enzyme for conversion...
Alzheimer's disease (AD) is characterized by both amyloid and Tau pathologies. The component altered cholesterol metabolism are closely linked, but the relationship between pathology currently unclear. Brain synthesized in situ cannot cross blood-brain barrier: to be exported from central nervous system into blood circuit, excess must converted 24S-hydroxycholesterol 24-hydroxylase encoded CYP46A1 gene. In AD patients, concentration of plasma cerebrospinal fluid lower than healthy controls....
Abstract Dysfunctions in brain cholesterol homeostasis have been extensively related to disorders. The main pathway for elimination is its hydroxylation into 24S-hydroxycholesterol by the 24-hydrolase, CYP46A1. Increasing evidence suggests that CYP46A1 has a role pathogenesis and progression of neurodegenerative disorders, increasing levels neuroprotective. However, mechanisms underlying this neuroprotection remain be fully understood. Huntington’s disease fatal autosomal dominant caused an...
The identification of the most efficient method for whole central nervous system targeting that is translatable to humans and safest route adeno-associated virus (AAV) administration a major concern future applications in clinics. Additionally, as many AAV serotypes were identified gene introduction into brain spinal cord, another key human gene-therapy success determine serotype. In this study, we compared lumbar intrathecal through catheter implantation intracerebroventricular cynomolgus...
Hematopoietic stem cell transplantation (HSCT) is a therapy used for multiple malignant and nonmalignant diseases, with chemotherapy pretransplantation myeloablation. The post-HSCT brain contains peripheral engrafted parenchymal macrophages, despite their absence in the normal brain, engraftment mechanism still undefined. Here we show that HSCT broadly disrupts mouse regenerative populations, including permanent loss of adult neurogenesis. Microglial density was halved, causing microglial...
In rodents, bone marrow-derived cells enter the brain during adult life. Allogeneic marrow transplantation is used to treat genetic CNS diseases, but fate of human and CD34 + within remains be elucidated. The present study demonstrates that derived from cells, isolated either cord blood or peripheral blood, migrate into after infusion nonobese diabetic/severe combined immunodeficient mice. Both types -derived differentiate perivascular ramified microglia. lentiviral transfer genes before...
Mammalian peroxisomal proteins adrenoleukodystrophy protein (ALDP), adrenoleukodystrophy-related (ALDRP), and 70-kDa (PMP70) belong to the superfamily of ATP-binding cassette (ABC) transporters. Unlike many ABC transporters that are single functional with two related halves, ALDP, ALDRP, PMP70 have structure half-transporters. The dysfunction ALDP is responsible for X-linked (X-ALD), a neurodegenerative disorder in which saturated very long-chain fatty acids accumulate because their impaired...
The L-pyruvate kinase (L-PK) gene is slightly active in normal and tumoral endocrine pancreatic tissues while, vivo, this not transcribed the exocrine pancreas. Nevertheless, L-PK re-expressed at a very low level cultured 266.6 cells derived from an pancreas carcinoma. early activated endodermal tissues, e.g. yolk sac primitive intestine; it remains fetal In adult, expression restricted to some cells. Hepatocyte nuclear factor (HNF) 1 HNF4 are main tissue-restricted transcription factors...