A5084572220- Amyotrophic Lateral Sclerosis Research
- Alzheimer's disease research and treatments
- Biochemical Acid Research Studies
- Neurological diseases and metabolism
- Cholinesterase and Neurodegenerative Diseases
- Neuroscience and Neuropharmacology Research
- Mitochondrial Function and Pathology
- Neurogenetic and Muscular Disorders Research
- Neuroinflammation and Neurodegeneration Mechanisms
University of Sheffield
2020-2024
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease involving selective vulnerability of energy-intensive motor neurons (MNs). It has been unclear whether mitochondrial function an upstream driver or downstream modifier neurotoxicity. We separated genetic determinants function, including variation within the genome autosomes; from changeable factors DNA copy number (mtCN). Across three cohorts 6,437 ALS patients, we discovered that set haplotypes, chosen because they are...
Mitochondrial dysfunction is a common feature of C9orf72 amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD); however, it remains unclear whether this cause or consequence the pathogenic process. Analysing multiple aspects mitochondrial biology across several Drosophila models -ALS/FTD, we found morphology, oxidative stress, and mitophagy are commonly affected, which correlated with progressive loss locomotor performance. Notably, only genetic manipulations that reversed stress...
Introduction: ALS is a neurodegenerative disorder characterised by progressive upper and lower motor neuron loss. A GGGGCC hexanucleotide repeat expansion (HRE) in the C9orf72 gene most common mutation found populations of European descent. Mitochondrial dysfunction has been observed C9orf72-ALS patients models disease, however reports on mitochondrial clearance via mitophagy are limited. Results: iNeurons from displayed reduced membrane potential mitophagy, due to reductions autophagosome...
Abstract Mitochondrial dysfunction such as excess production of reactive oxygen species (ROS) and defective mitochondrial dynamics are common features C9orf72 Amyotrophic Lateral Sclerosis/Frontotemporal Dementia (ALS/FTD), but it remains unclear whether these causative or a consequence the pathogenic process. To address this, we have performed comprehensive characterisation in vivo model, analysing multiple transgenic Drosophila models -related pathology, which can be correlated to...