A5078496069- Alzheimer's disease research and treatments
- Nuclear Receptors and Signaling
- Amyotrophic Lateral Sclerosis Research
- Circadian rhythm and melatonin
- Cellular transport and secretion
- Cephalopods and Marine Biology
- Photoreceptor and optogenetics research
- Lysosomal Storage Disorders Research
- Autophagy in Disease and Therapy
- Animal Genetics and Reproduction
- Olfactory and Sensory Function Studies
- Computational Drug Discovery Methods
- Sleep and Wakefulness Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Epilepsy research and treatment
- Neurological diseases and metabolism
- Genetic Neurodegenerative Diseases
- Pharmacological Effects and Toxicity Studies
- Parkinson's Disease Mechanisms and Treatments
- Genetics, Aging, and Longevity in Model Organisms
- CRISPR and Genetic Engineering
- Light effects on plants
- Metabolism and Genetic Disorders
- Nerve injury and regeneration
- Pain Mechanisms and Treatments
Royal Veterinary College
2020
University College London
2013-2018
National Hospital for Neurology and Neurosurgery
2013-2018
RIKEN Center for Brain Science
2017
The Ohio State University
2013-2016
University of Miami
1989
Dipeptide repeat peptides on the attack Certain neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), are associated with expanded dipeptides translated from RNA transcripts of disease-associated genes (see Perspective by West and Gitler). Kwon et al. show that encoded repeats in C9orf72 gene interfere way cells make kill cells. These effects may account for how this genetic form ALS causes disease. Working Drosophila , Mizielinska aimed to distinguish between...
An expanded GGGGCC repeat in a non-coding region of the C9orf72 gene is common cause frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis. Non-coding expansions may disease by reducing expression level they reside in, producing toxic aggregates RNA termed foci, or proteins generated repeat-associated non-ATG translation. We present first definitive report sense antisense foci using series C9FTLD cases, neurodegenerative normal controls. A sensitive specific fluorescence...
A large body of literature has shown that the disruption circadian clock timing profound effects on mood, memory and complex thinking. Central to this time keeping process is master pacemaker located within suprachiasmatic nucleus (SCN). Of note, central nervous system, not exclusive SCN, but rather, ancillary oscillatory capacity been detected in a wide range cell types brain regions, including forebrain circuits underlie cognitive processes. These observations raise questions about...
Mutations in the charged multivesicular body protein 2B (CHMP2B) cause frontotemporal dementia (FTD). We report that mice which express FTD-causative mutant CHMP2B at physiological levels develop a novel lysosomal storage pathology characterised by large neuronal autofluorescent aggregates. The aggregates are an early and progressive occur 3 months of age increase both size number over time. These not observed expressing wild-type CHMP2B, or non-transgenic controls, indicating they specific...
Small cells called microglia, which collect at nerve lesions, were tracked as they moved within the leech cord to crushes made minutes or hours before. The aim of this study was determine whether microglia respond a group and move en masse instead individually, different rates, along axons directly lesion take another route, such edges cord. Cell nuclei in living cords stained with Hoechst 33258 dye observed under dim ultraviolet illumination using fluorescence optics, low-light video...
The CREB/CRE transcriptional pathway has been implicated in circadian clock timing and light-evoked resetting. To date, much of the work on CREB physiology focused how changes phosphorylation state regulate processes. However, beyond phosphorylation, CREB-dependent transcription can also be regulated by coactivator CRTC (CREB-regulated coactivator), known as TORC (transducer CREB). Here we profiled both rhythmic regulation CRTC1 CRTC2 murine suprachiasmatic nucleus (SCN), locus master...
Mutations in the endosome-associated protein CHMP2B cause frontotemporal dementia and lead to lysosomal storage pathology neurons. We here report that physiological levels of mutant causes reduced numbers significantly impaired trafficking endolysosomes within neuronal dendrites, accompanied by increased dendritic branching. Mechanistically, this is due stable incorporation onto endolysosomes, which we show renders them unable traffic dendrites. This defect inability recruit ATPase VPS4,...
Frontotemporal dementia (FTD)-causing mutations in the CHMP2B gene lead to generation of mutant C-terminally truncated CHMP2B. We report that transgenic mice expressing endogenous levels developed late-onset brain volume loss associated with frank neuronal and FTD-like changes social behaviour. These data are first show neurodegeneration indicate our mouse model is able recapitulate neurodegenerative observed FTD. Neuroinflammation has been increasingly implicated neurodegeneration,...
Background: Transgenic animal models are a widely used and powerful tool to investigate human disease develop therapeutic interventions. Making transgenic mouse involves random integration of exogenous DNA into the host genome that can have effect disrupting endogenous gene expression. The J20 model Alzheimer's (AD) is overexpresser APP with familial AD mutations has been extensively utilised in preclinical studies our aim was determine genomic location transgene insertion. Methods: We...
<ns4:p><ns4:bold>Background: </ns4:bold>Transgenic animal models are a widely used and powerful tool to investigate human disease develop therapeutic interventions. Making transgenic mouse involves random integration of exogenous DNA into the host genome that can have effect disrupting endogenous gene expression. The J20 model Alzheimer’s (AD) is overexpresser APP with familial AD mutations has been extensively utilised in preclinical studies our aim was determine genomic location transgene...
Background Structural epilepsy in dogs is often treated medically with a combination of antiseizure drugs (ASDs) and other concurrent therapies for the primary condition. Unlike idiopathic epilepsy, there have been few studies on efficacy medical management structural epilepsy. This study investigated factors affecting treatment outcomes managed Methods Cases 71 diagnosed were identified from referral hospital database data analysed retrospectively. Efficacy was assessed by survival time,...