Marcus Keatinge
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View article: Activity-driven myelin sheath growth is mediated by mGluR5
Activity-driven myelin sheath growth is mediated by mGluR5 Open
Myelination by oligodendrocytes in the central nervous system is influenced by neuronal activity, but the molecular mechanisms by which this occurs have remained unclear. Here we employed pharmacological, genetic, functional imaging and op…
View article: Interleukin-34 orchestrates bone formation through its binding to Bone Morphogenic Proteins
Interleukin-34 orchestrates bone formation through its binding to Bone Morphogenic Proteins Open
During growth, the contribution of IL34, a ligand of MCSFR, have not been established. The aim of this work was therefore to establish these implications using two models of IL34 invalidation generated in zebrafish and mouse. Significant g…
View article: C9ORF72 Deficiency Results in Neurodegeneration in the Zebrafish Retina
C9ORF72 Deficiency Results in Neurodegeneration in the Zebrafish Retina Open
Hexanucleotide repeat expansions within the gene C9ORF72 are the most common cause of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). This disease-causing expansion leads to a reduction…
View article: C9ORF72 deficiency results in degeneration of the zebrafish retina<i>in vivo</i>
C9ORF72 deficiency results in degeneration of the zebrafish retina<i>in vivo</i> Open
G4C2 Hexanucleotide repeat expansions within the gene C9ORF72 are the most common cause of the neurodegenerative diseases Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal dementia (FTD). This disease-causing expansion leads to a redu…
View article: Unexpected phenotypic and molecular changes of combined glucocerebrosidase and acid sphingomyelinase deficiency
Unexpected phenotypic and molecular changes of combined glucocerebrosidase and acid sphingomyelinase deficiency Open
Heterozygous variants in GBA1, encoding glucocerebrosidase (GCase), are the most common genetic risk factor for Parkinson's disease (PD). Moreover, sporadic PD patients also have a substantial reduction of GCase activity. Genetic variants …
View article: Ankk1 Loss of Function Disrupts Dopaminergic Pathways in Zebrafish
Ankk1 Loss of Function Disrupts Dopaminergic Pathways in Zebrafish Open
Ankyrin repeat and kinase domain containing 1 (ANKK1) is a member of the receptor-interacting protein serine/threonine kinase family, known to be involved in cell proliferation, differentiation and activation of transcription factors. Gene…
View article: CRISPR gRNA phenotypic screening in zebrafish reveals pro-regenerative genes in spinal cord injury
CRISPR gRNA phenotypic screening in zebrafish reveals pro-regenerative genes in spinal cord injury Open
Zebrafish exhibit robust regeneration following spinal cord injury, promoted by macrophages that control post-injury inflammation. However, the mechanistic basis of how macrophages regulate regeneration is poorly understood. To address thi…
View article: Acid Sphingomyelinase Deficiency Normalizes Neuronal Function in GCase Deficiency - Unexpected Biological Rescue Effect of Combined Genetic Risk Factors for Parkinson’s Disease
Acid Sphingomyelinase Deficiency Normalizes Neuronal Function in GCase Deficiency - Unexpected Biological Rescue Effect of Combined Genetic Risk Factors for Parkinson’s Disease Open
Background The additive mechanistic effect of genetic risk variants for Parkinson’s disease (PD) is a plausible but largely unproven hypothesis. We investigated the mechanistic interaction between the two lysosomal PD risk genes glucocereb…
View article: RNA-seq analysis and compound screening highlight multiple signalling pathways regulating secondary cell death after acute CNS injury<i>in vivo</i>
RNA-seq analysis and compound screening highlight multiple signalling pathways regulating secondary cell death after acute CNS injury<i>in vivo</i> Open
Understanding the molecular mechanisms that regulate secondary cell death after acute central nervous system (CNS) injury is critical for the development of effective neuroprotective drugs. Previous research has shown that neurotoxic proce…
View article: Phenotypic screening using synthetic CRISPR gRNAs reveals pro-regenerative genes in spinal cord injury
Phenotypic screening using synthetic CRISPR gRNAs reveals pro-regenerative genes in spinal cord injury Open
Acute CRISPR/Cas9 targeting offers the opportunity for scalable phenotypic genetic screening in zebrafish. However, the unpredictable efficiency of CRISPR gRNA (CrRNA) activity is a limiting factor. Here we describe how to resolve this by …
View article: Brain tumours repurpose endogenous neuron to microglia signalling mechanisms to promote their own proliferation
Brain tumours repurpose endogenous neuron to microglia signalling mechanisms to promote their own proliferation Open
Previously we described direct cellular interactions between microglia and AKT1+ brain tumour cells in zebrafish (Chia et al., 2018). However, it was unclear how these interactions were initiated: it was also not clear if they had an impac…
View article: Unexpected opposing biological effect of genetic risk factors for Parkinson’s disease
Unexpected opposing biological effect of genetic risk factors for Parkinson’s disease Open
The additive effect of genetic risk variants on overall disease risk is a plausible but frequently unproven hypothesis. To test this hypothesis, we assessed the biological effect of combined glucocerebrosidase (GCase) and acid sphingomyeli…
View article: Rapid clearance of cellular debris by microglia limits secondary neuronal cell death after brain injury <i>in vivo</i>
Rapid clearance of cellular debris by microglia limits secondary neuronal cell death after brain injury <i>in vivo</i> Open
Moderate or severe traumatic brain injury (TBI) causes widespread neuronal cell death. Microglia, the resident macrophages of the brain, react to injury by migrating to the lesion site, where they phagocytose cellular debris. Microglial ph…
View article: Restriction of mitochondrial calcium overload by <i>mcu</i> inactivation renders neuroprotective effect in Zebrafish models of Parkinson's disease
Restriction of mitochondrial calcium overload by <i>mcu</i> inactivation renders neuroprotective effect in Zebrafish models of Parkinson's disease Open
The loss of dopaminergic neurons (DA) is a pathological hallmark of sporadic and familial forms of Parkinson's Disease (PD). We had previously shown that inhibiting mitochondrial calcium uniporter (mcu) using morpholinos can rescue DA neur…
View article: Dynamic control of proinflammatory cytokines Il-1β and Tnf-α by macrophages in zebrafish spinal cord regeneration
Dynamic control of proinflammatory cytokines Il-1β and Tnf-α by macrophages in zebrafish spinal cord regeneration Open
Spinal cord injury leads to a massive response of innate immune cells in non-regenerating mammals, but also in successfully regenerating zebrafish. However, the role of the immune response in successful regeneration is poorly defined. Here…
View article: The NAD+ Precursor Nicotinamide Riboside Rescues Mitochondrial Defects and Neuronal Loss in iPSC and Fly Models of Parkinson’s Disease
The NAD+ Precursor Nicotinamide Riboside Rescues Mitochondrial Defects and Neuronal Loss in iPSC and Fly Models of Parkinson’s Disease Open
While mitochondrial dysfunction is emerging as key in Parkinson's disease (PD), a central question remains whether mitochondria are actual disease drivers and whether boosting mitochondrial biogenesis and function ameliorates pathology. We…
View article: Dynamic control of proinflammatory cytokines Il-1β and Tnf-α by macrophages is necessary for functional spinal cord regeneration in zebrafish
Dynamic control of proinflammatory cytokines Il-1β and Tnf-α by macrophages is necessary for functional spinal cord regeneration in zebrafish Open
Spinal cord injury leads to a massive response of innate immune cells (microglia, macrophages, neutrophils) both, in non-regenerating mammals and in successfully regenerating zebrafish, but the role of these immune cells in functional spin…
View article: Inhibition of the mitochondrial calcium uniporter rescues dopaminergic neurons in <i>pink1</i><sup><i>−</i>/<i>−</i></sup> zebrafish
Inhibition of the mitochondrial calcium uniporter rescues dopaminergic neurons in <i>pink1</i><sup><i>−</i>/<i>−</i></sup> zebrafish Open
Mutations in PTEN ‐induced putative kinase 1 ( PINK 1 ) are a cause of early onset Parkinson's disease ( PD ). Loss of PINK 1 function causes dysregulation of mitochondrial calcium homeostasis, resulting in mitochondrial dysfunction and ne…