A5024476885- Genetic Neurodegenerative Diseases
- Pluripotent Stem Cells Research
- Parkinson's Disease Mechanisms and Treatments
- Neurological disorders and treatments
- Nerve injury and regeneration
- CRISPR and Genetic Engineering
- Neuroscience and Neuropharmacology Research
- Alzheimer's disease research and treatments
- Memory and Neural Mechanisms
- Neurogenesis and neuroplasticity mechanisms
- Stress Responses and Cortisol
- Neuroscience and Neural Engineering
- Nuclear Receptors and Signaling
- Mitochondrial Function and Pathology
- Botulinum Toxin and Related Neurological Disorders
- Neurotransmitter Receptor Influence on Behavior
- Regulation of Appetite and Obesity
- Fluorine in Organic Chemistry
- Cellular transport and secretion
- Adrenal Hormones and Disorders
- Melanoma and MAPK Pathways
- Animal Genetics and Reproduction
- Caveolin-1 and cellular processes
- RNA Interference and Gene Delivery
- Cardiac and Coronary Surgery Techniques
Cardiff University
2013-2025
Stem cell treatments for neurodegenerative diseases are expected to reach clinical trials soon. Most of the approaches currently under development involve transplantation immature progenitors that subsequently undergo phenotypic and functional maturation in vivo, predicting long-term graft outcome already at progenitor stage remains a challenge. Here, we took an unbiased approach identify predictive markers expressed dopamine neuron correlate with animal model Parkinson's disease through...
Medium-sized spiny neurons (MSNs) are the only neostriatum projection neurons, and their degeneration underlies some of clinical features Huntington’s disease. Using knowledge human developmental biology exposure to key neurodevelopmental molecules, pluripotent stem (hPS) cells were induced differentiate into MSNs. In a feeder-free adherent culture, ventral telencephalic specification is by BMP/TGFβ inhibition subsequent SHH/DKK1 treatment. The emerging FOXG1+/GSX2+ progenitors then...
Transplantation of human induced pluripotent stem cell-derived dopaminergic (iPSC-DA) neurons is a promising therapeutic strategy for Parkinson's disease (PD). To assess optimal cell characteristics and reproducibility, we evaluated the efficacy iPSC-DA neuron precursors from two individuals with sporadic PD by transplantation into hemiparkinsonian rat model after differentiation either 18 (d18) or 25 days (d25). We found similar graft size dopamine (DA) content in both groups, but only d18...
Abstract Cell signaling is central to neuronal activity and its dysregulation may lead neurodegeneration cognitive decline. Here, we show that selective genetic potentiation of ERK prevents cell death in vitro vivo the mouse brain, while attenuation does opposite. This neuroprotective effect mediated by an enhanced nuclear can also be induced novel penetrating peptide RB5. In administration RB5 disrupts preferential interaction ERK1 MAP kinase with importinα1/KPNA2 over ERK2, facilitates...
Abstract Expanded CAG/CTG repeats cause at least 15 different neurodegenerative and neuromuscular diseases that all remain without an effective disease modifying treatment. Because the size of repeat tract accounts for majority variation in severity, contracting them presents attractive therapeutic avenue. Here, we show CRISPR-Cas9 nickase targeting itself leads to efficient contractions Huntington’s patient-derived neurons astrocytes, as well myotonic dystrophy type 1 neurons. Using...
Patients suffering from Parkinson's disease (PD) display cognitive and neuropsychiatric dysfunctions, especially with progression. Although these impairments have been reported to impact more heavily upon a patient's quality of life than any motor there are currently no interventions capable adequately targeting non-motor deficits. Utilizing rodent model PD, we investigated whether cell replacement therapy, using intrastriatal transplants human-derived ventral mesencephalic (hVM) grafts,...
Huntington's disease (HD) is an incurable neurodegenerative disorder which causes a triad of motor, cognitive and psychiatric disturbances. Cognitive disruptions are core feature the disease, significantly affect daily activities quality life, therefore training interventions present exciting therapeutic intervention possibility for HD. We aimed to determine if specific training, in operant task attention, modifies subsequent behavioural neuropathological phenotype Hdh(Q111) mouse model...
Huntington's disease (HD) is a debilitating, genetically inherited neurodegenerative disorder that results in early loss of medium spiny neurons from the striatum and subsequent degeneration cortical other subcortical brain regions. Behavioral changes manifest as range motor, cognitive, neuropsychiatric impairments. It has been established replacement degenerated with rat-derived fetal whole ganglionic eminence (rWGE) tissue can alleviate motor cognitive deficits preclinical rodent models...
The onset of Alzheimer's disease (AD) is often accompanied by changes in emotion, motivation, and goal-directed behavior. production beta-amyloid thought to be a major early contributor the pathogenesis AD. present study tested hypothesis that amyloid pathology amygdala, frontal cortex, hippocampus Tg2576 mice would disrupt development instrumental- and/or Pavlovian-outcome associations. results showed both Pavlovian-conditioned behaviors were sensitive outcome devaluation (Experiments 1 &...
Abstract Although episodic memory deficits are the most conspicuous cognitive change in patients with Alzheimer's disease ( AD ), also display alterations emotional expression, including anxiety and impaired conditioned fear behaviours. The neural circuitry underlying learning is known to involve amygdala hippocampus, although precise impact of amyloid pathology on interaction between these brain regions remains unclear. Recent evidence suggests that Tg2576 mice, which express a human...
ABSTRACT Background The risk of graft‐induced dyskinesias (GIDs) presents a major challenge in progressing cell transplantation as therapy for Parkinson's disease. Current theories implicate the presence grafted serotonin neurons, hotspots dopamine release, neuroinflammation and established levodopa‐induced dyskinesia. Objective To elucidate mechanisms GIDs. Methods Neonatally desensitized, denervated rats received intrastriatal grafts human embryonic stem cells (hESCs) differentiated into...