A5074464568- Parkinson's Disease Mechanisms and Treatments
- Nuclear Receptors and Signaling
- Pluripotent Stem Cells Research
- Autism Spectrum Disorder Research
- Neurogenesis and neuroplasticity mechanisms
- Nerve injury and regeneration
- CRISPR and Genetic Engineering
- Neurological disorders and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Virus-based gene therapy research
- Olfactory and Sensory Function Studies
- Health Systems, Economic Evaluations, Quality of Life
- Iron Metabolism and Disorders
- Genetic Neurodegenerative Diseases
- Zebrafish Biomedical Research Applications
- Neurological diseases and metabolism
- RNA Interference and Gene Delivery
- RNA regulation and disease
- Mesenchymal stem cell research
- Inflammation biomarkers and pathways
- Single-cell and spatial transcriptomics
- Lysosomal Storage Disorders Research
- Genetics and Neurodevelopmental Disorders
- Animal Genetics and Reproduction
- Family Support in Illness
Parkinson's UK
2021-2025
Inserm
2024
Research Network (United States)
2024
French Clinical Research Infrastructure Network
2024
Université de Bordeaux
2024
University of Calabar
2023
Cure Parkinson's Trust
2019-2022
University of Cambridge
2013-2022
Wellcome/MRC Cambridge Stem Cell Institute
2020-2022
The Francis Crick Institute
2013-2017
Understanding human embryonic ventral midbrain is of major interest for Parkinson's disease. However, the cell types, their gene expression dynamics, and relationship to commonly used rodent models remain be defined. We performed single-cell RNA sequencing examine development in mouse. found 25 molecularly defined including five subtypes radial glia-like cells four progenitors. In mouse, two mature fetal dopaminergic neuron diversified into adult classes during postnatal development. Cell...
BackgroundLixisenatide, a glucagon-like peptide-1 receptor agonist used for the treatment of diabetes, has shown neuroprotective properties in mouse model Parkinson's disease.MethodsIn this phase 2, double-blind, randomized, placebo-controlled trial, we assessed effect lixisenatide on progression motor disability persons with disease. Participants whom disease was diagnosed less than 3 years earlier, who were receiving stable dose medications to treat symptoms, and did not have complications...
Since 2020, annual reports on the clinical development of new drug-based therapies for neurodegenerative condition Parkinson's disease (PD) have been generated. These reviews followed progress both "symptomatic treatments" (ST - improves/reduces symptoms condition) and "disease modifying (DMT attempts to delay/slow progression by addressing underlying biology PD). Additional efforts made further categorize these experimental treatments based their mechanisms action class drug.A dataset...
The specification and differentiation of dentate gyrus granule neurons in the hippocampus require temporally spatially coordinated actions both intrinsic extrinsic molecules. basic helix-loop-helix transcription factor Neurogenin2 (Ngn2) NeuroD1 are key regulators these processes. Based on existing classification, we analyzed molecular events occurring during hippocampal neurogenesis, primarily focusing juvenile animals. We found that Ngn2 is transiently expressed by late type-2a amplifying...
The 6-hydroxydopamine (6-OHDA) neurotoxic lesion of the midbrain dopamine (DA) system is one most widely used techniques for modelling Parkinson's disease in rodents. majority studies using this approach, however, largely limit their analysis to lesioning acutely, and looking at behavioural deficits number surviving tyrosine hydroxylase (TH)-stained cells midbrain. Here we have analysed additional characteristics that occur following intrastriatal delivery 6-OHDA, providing better...
Neuroinflammation and activation of innate immunity are early events in neurodegenerative diseases including Alzheimer's disease (AD). Recently, a rare mutation the gene Triggering receptor expressed on myeloid cells 2 (TREM2) has been associated with substantial increase risk develo ping late onset AD. To uncover molecular mechanisms underlying this association, we investigated RNA protein expression TREM2 APP/PS1 transgenic mice. Our findings suggest that not only plays critical role...
The maintained expression of transcription factors throughout the development mesodiencephalic dopaminergic (mDA) neurons suggests multiple roles at various stages in development. Two members forkhead/winged helix factor family, Foxa1 and Foxa2, have been recently shown to an important influence early mDA neurons. Here we present data demonstrating that these genes are also involved later maintenance system. We conditionally removed both postmitotic using dopamine transporter-cre mouse....
Hepcidin is a peptide hormone belonging to the defensin family of cationic antimicrobial molecules that has an essential role in systemic iron homeostasis. The synthesised by hepatocytes and transported circulation target tissues where it regulates export function ferrous permease, ferroportin. In brain hepcidin protein been identified using immuno-histochemistry mRNA real-time PCR but not situ hybridisation raising question whether there measurable transcription gene central nervous system....
Abstract An increase in the efficiency of clinical trial conduct has been successfully demonstrated oncology field, by use multi-arm, multi-stage trials allowing evaluation multiple therapeutic candidates simultaneously, and seamless recruitment to phase 3 for those passing an interim signal efficacy. Replicating this complex innovative design diseases such as Parkinson’s disease is appealing, but addition challenges associated with any assessing a single potentially modifying intervention...
Abstract The stage‐specific embryonic antigen 4 (SSEA4) is commonly used as a cell surface marker to identify the pluripotent human stem (ES) cells. Immunohistochemistry on central nervous system revealed that SSEA4 detectable in early neuroepithelium, and its expression decreases development proceeds. Flow cytometry analysis of forebrain‐derived cells demonstrated SSEA4‐expressing are enriched neural stem/progenitor fraction (CD133 + ), but rarely codetected with (NSC) CD15. Using...
Significant efforts are ongoing to develop refined differentiation protocols generate midbrain dopamine (DA) neurons from pluripotent stem cells for application in disease modeling, diagnostics, drug screening and cell-based therapies Parkinson's disease. An increased understanding of the timing molecular mechanisms that promote generation distinct subtypes human DA during development will be essential guiding future molecularly defined subtype-specific cells. Here, we use droplet-based...
Midbrain dopaminergic neurons are highly heterogeneous. They differ in their connectivity and firing patterns and, therefore, functional properties. The molecular underpinnings of this heterogeneity largely unknown, there is a paucity markers that distinguish these subsets. In paper, we report the identification characterization novel subset midbrain located ventral tegmental area expresses basic helix-loop-helix transcription factor, Neurogenic Differentiation Factor-6 (NEUROD6). Retrograde...
Background: Down syndrome (DS; trisomy 21) individuals have a spectrum of hematopoietic and neuronal dysfunctions by the time they reach age 40 years, almost all develop Alzheimer’s disease (AD) neuropathology which includes senile plaques neurofibrillary tangles. Inflammation innate immunity are key players in AD DS. Triggering receptor expressed myeloid cells-2 (TREM2) variants been identified as risk factors for other neurodegenerative diseases. Objective: To investigate effects TREM2...
Central administration of N-terminal tripeptide IGF-1 (GPE) prevents the loss dopamine neurons. We now examine effects GPE administered peripherally, on long-term functional recovery after 6-OHDA lesion in rats. treatment (3 mg/kg, i.p.), 3 days reduced number rotations (p<0.005) and time over meter compared to vehicle treatment. Step length adjusting steps were increased group (p<0.005), particularly at 12 weeks post lesion. However, did not prevent tyrosine hydroxylase substantia nigra...
The field of Parkinson's disease research has been impeded by the absence animal models that clearly phenocopy features this neurodegenerative condition. Mutations in FBXO7/PARK15 are associated with both sporadic and a severe form autosomal recessive early-onset Parkinsonism. Here we report conditional deletion Fbxo7 midbrain dopamine neurons results an early reduction striatal levels, together slow, progressive loss onset locomotor defects. Unexpectedly, later compensatory response led to...