A5002900522- Retinal Diseases and Treatments
- Alzheimer's disease research and treatments
- Neurological Disorders and Treatments
- Neurological Disease Mechanisms and Treatments
- Cell Image Analysis Techniques
- Neurogenetic and Muscular Disorders Research
- Neuroscience and Neuropharmacology Research
- Advanced Fluorescence Microscopy Techniques
- Retinal Development and Disorders
- Receptor Mechanisms and Signaling
- Amyotrophic Lateral Sclerosis Research
- Bioinformatics and Genomic Networks
- Biomarkers in Disease Mechanisms
- Estrogen and related hormone effects
- Retinal and Optic Conditions
- Apelin-related biomedical research
- Cancer-related Molecular Pathways
- Nerve injury and regeneration
- Glaucoma and retinal disorders
- MRI in cancer diagnosis
- Cholinesterase and Neurodegenerative Diseases
- Pluripotent Stem Cells Research
- Ocular Oncology and Treatments
- Genomic variations and chromosomal abnormalities
- Retinal Imaging and Analysis
King's College London
2020-2024
University College London
2015-2024
Northwestern University
2006-2012
Evanston Hospital
2008
β-Site amyloid precursor protein cleaving enzyme 1 (BACE1) (β-secretase) initiates generation of β-amyloid (Aβ), which plays an early role in Alzheimer's disease (AD). BACE1 levels are increased postmortem AD brain, suggesting elevation promotes Aβ production and AD. Alternatively, the increase may be epiphenomenon late-stage To distinguish between these possibilities, we analyzed using a highly specific antibody, BACE-Cat1, made BACE1−/− mice, mount robust anti-BACE1 immune response....
We provide microarray data comparing genome-wide differential expression and pathology throughout life in four lines of "amyloid" transgenic mice (mutant human APP, PSEN1, or APP/PSEN1) "TAU" MAPT gene). Microarray were validated by qPCR comparison to studies, including association study (GWAS) hits. Immune gene correlated tightly with plaques whereas synaptic genes negatively neurofibrillary tangles. Network analysis immune modules revealed six hub hippocampus amyloid mice, common cortex....
Epac2 disruption impairs basal (but not apical) dendrite complexity in cortical neurons, and an autism-associated mutation implicates a Ras/Epac2 signaling pathway the active maintenance of dendritic arbors.
Detecting and treating Alzheimer’s disease, before cognitive deficits occur, has become the health challenge of our time. The earliest known event in disease is rising amyloid-β. Previous studies have suggested that effects on synaptic transmission may precede plaque deposition. Here we report how relative levels different soluble amyloid-β peptides hippocampus, preceding deposition, relate to genomic changes. Immunoprecipitation-mass spectrometry was used measure early rise a mouse model...
Mutations in the ALS2 gene result early-onset amyotrophic lateral sclerosis, infantile-onset ascending hereditary spastic paraplegia and juvenile primary suggesting prominent upper motor neuron involvement. However, importance of alsin function for corticospinal (CSMN) health stability remains unknown. To date, four separate knockout (AlsinKO) mouse models have been generated, despite hopes mimicking human pathology, none displayed profound defects. This, however, does not rule out...
Understanding mechanisms that lead to selective motor neuron degeneration requires visualization and cellular identification of vulnerable neurons. Here we report generation characterization UCHL1-eGFP hSOD1 G93A - UeGFP mice, novel reporter lines for cortical spinal Corticospinal neurons (CSMN) a subset (SMN) are genetically labeled in which express eGFP under the UCHL1 promoter. expression is stable continues through P800 vivo . Retrograde labeling, molecular marker expression,...
Diabetic retinopathy (DR), a common diabetes complication leading to vision loss, presents early clinical signs linked retinal vasculature damage, affecting the neural retina at advanced stages. However, vascular changes and potential effects on cells before diagnosis of DR are less well understood. To study earliest stages DR, we performed histological phenotyping quantitative analysis postmortem retinas from 10 donors with without (e.g., microaneurysms, hemorrhages), plus three control...
The inability to observe relevant biological processes in vivo significantly restricts human neurodevelopmental research. Advances appropriate vitro model systems, including patient-specific brain organoids and cortical spheroids (hCSs), offer a pragmatic solution this issue. In particular, hCSs are an accessible method for generating homogenous of dorsal telencephalic fate, which recapitulate key aspects corticogenesis, the formation neural rosettes-in correlates tube. These neurogenic...
Invasion of pigmented cells into the retina occurs in retinal degenerative diseases, such as macular telangiectasia type 2 (MacTel) and retinitis pigmentosa (RP). These intraretinal may be derived from pigment epithelium (RPE), but differences similarities between RPE have so far not been well characterised.Clinicopathologic case report.Here, we compared with by immunohistochemistry. Immunohistological stains for classic markers (RPE65, CRALBP KRT18) blood vessel (lectin collagen 4) were...
Negative regulator of ubiquitin-like protein 1 (NUB1) and its longer isoform NUB1L are (UBL)/ubiquitin-associated (UBA) proteins that facilitate the targeting proteasomal substrates, including tau, synphilin-1 huntingtin. Previous data revealed NUB1 also mediated a reduction in tau phosphorylation aggregation following proteasome inhibition, suggesting switch function from targeted degradation to role autophagy. Here, we delineate mechanisms this show interacted specifically with p62 induced...
ABSTRACT Aim Diabetic retinopathy (DR) is a common complication of diabetes mellitus and can result in vision loss. Early clinically diagnosed signs DR are linked to vascular damage, impacting on the neural retina typically at later stages. However, changes potential effects cells before clinical diagnosis less understood. Methods To learn more about earliest stages we studied postmortem from diabetic donors who did not have DR. Histological phenotyping quantitative analysis were carried out...
<p dir="ltr">Diabetic retinopathy (DR), a common diabetes complication leading to vision loss, presents early clinical signs linked retinal vasculature damage, affecting the neural retina at advanced stages. However, vascular changes and potential effects on cells before diagnosis of DR are less well understood. To study earliest stages we performed histological phenotyping quantitative analysis postmortem retinas from 10 donors with without (such as microaneurysms haemorrhages), plus...
<p dir="ltr">Diabetic retinopathy (DR), a common diabetes complication leading to vision loss, presents early clinical signs linked retinal vasculature damage, affecting the neural retina at advanced stages. However, vascular changes and potential effects on cells before diagnosis of DR are less well understood. To study earliest stages we performed histological phenotyping quantitative analysis postmortem retinas from 10 donors with without (such as microaneurysms haemorrhages), plus...
Abstract Estrogens, specifically 17β-estradiol (estradiol), can modulate synaptic function by regulating the expression and localisation of proteins. However, mechanisms underlying estradiol’s regulation protein expression, whether if they occur in a sex specific manner, is not well understood. In this study, using sex-specific hippocampal slice cultures mixed-sex primary neurons, we investigated local synthesis required for estradiol- induced expression. Estradiol rapidly increased rate...
Although successful visualization of amyloid deposits in the APP transgenic mouse brain with MR imaging has been reported recently, there is no suitable method to measure plaque load (PL). We present a novel based on simulated flooding (watersheds) segment plaques images. In this method, image segmented into catchment basins (CB) associated local minima and CBs that correspond are selected using data Laplacian as feature describing variation. Besides PL (volume fraction) estimation, our can...
Although successful visualization of amyloid deposits in the APP transgenic mouse brain with MR imaging has been reported recently, there is no suitable method to measure plaque load (PL). We present a novel based on simulated flooding (watersheds) segment plaques images. In this method, image segmented into catchment basins (CB) associated local minima and CBs that correspond are selected using data Laplacian as feature describing variation. Besides PL (volume fraction) estimation, our can...
Abstract Background The inability to observe relevant biological processes in vivo significantly restricts human neurodevelopmental research. Advances appropriate vitro model systems, including patient-specific brain organoids and Cortical Spheroids (hCSs) offer a pragmatic solution this issue. In particular, hCSs are an accessible method of generating homogenous dorsal telencephalic fate, which recapitulate key aspects corticogenesis, the formation neural rosettes. These neurogeneic niches...