A5101859623- Prion Diseases and Protein Misfolding
- Neurological diseases and metabolism
- Trace Elements in Health
- Alcoholism and Thiamine Deficiency
- Functional Brain Connectivity Studies
- Alzheimer's disease research and treatments
- Amino Acid Enzymes and Metabolism
- Health and Wellbeing Research
- Biochemical Acid Research Studies
- BRCA gene mutations in cancer
- Computational Drug Discovery Methods
- Cholinesterase and Neurodegenerative Diseases
- Cancer Treatment and Pharmacology
- Neural and Behavioral Psychology Studies
- Hepatitis B Virus Studies
- Vaccine Coverage and Hesitancy
- Nuclear Receptors and Signaling
- Multisensory perception and integration
- Schizophrenia research and treatment
- Gestational Diabetes Research and Management
- Genomics and Chromatin Dynamics
- Radiopharmaceutical Chemistry and Applications
- Cancer, Hypoxia, and Metabolism
- Hepatitis C virus research
- Religion, Spirituality, and Psychology
University College London
2023-2025
MRC Prion Unit
2022-2025
Medical Research Council
2023-2025
VIB-KU Leuven Center for Brain & Disease Research
2022
Medical University of South Carolina
2007
North Carolina State University
1991
Harbor–UCLA Medical Center
1990
Familial Alzheimer's disease (FAD), caused by mutations in Presenilin (PSEN1/2) and Amyloid Precursor Protein (APP) genes, is associated with an early age at onset (AAO) of symptoms. AAO relatively consistent within families between carriers the same mutations, but differs markedly individuals carrying different mutations. Gaining a mechanistic understanding why certain manifest several decades earlier than others extremely important elucidating foundations pathogenesis AAO. Pathogenic...
Twenty-four patients who developed their first psychotic episode after the age of 45 were studied with MRI and comprehensive neuropsychological testing compared 72 healthy elderly subjects. The demonstrated more clinical abnormalities on MRI, likely to have large white-matter lesions or metabolic illness, did poorly many tests, particularly those frontal-lobe memory abilities. We conclude that structural brain injury is commonly associated late onset psychosis. Neuroimaging investigations...
Changes with age in cognitive abilities subserved by the frontal lobes have not been well studied, and existing research has contradictory, possibly due to uncontrolled effects of medical psychiatric illness. The purpose this study was compare performance healthy middle‐aged older individuals on four lobe tests (Wisconsin Card Sorting Test, Stroop Auditory Consonant Trigrams, Verbal Fluency) provide information regarding differences abilities. Data were obtained 61 screened for absence...
In a prospective study of late-life onset psychosis, five the first 27 patients studied had extensive white-matter lesions demonstrated by MRI and/or CT. None 60 age-matched psychiatrically healthy controls such lesions. All mild dementia and frontal behavioural syndrome. addition, every patient performed poorly on neuropsychological tests function. Dysfunction cortex associated with appears to contribute clinical picture some cases psychosis.
Prions replicate via the autocatalytic conversion of cellular prion protein (PrP C ) into fibrillar assemblies misfolded PrP. While this process has been extensively studied in vivo and vitro, non-physiological reaction conditions fibril formation vitro have precluded identification mechanistic analysis proteins, which may alter PrP self-assembly replication. Here, we developed a assay for recombinant murine human (23-231) under near-native (NAA) to study effect be risk factors or potential...
Abstract Prions are assemblies of misfolded prion protein that cause several fatal and transmissible neurodegenerative diseases, with the most common phenotype in humans being sporadic Creutzfeldt-Jakob disease (sCJD). Aside from variation itself, molecular risk factors not well understood. Prion prion-like mechanisms thought to underpin disorders meaning elucidation could have broad relevance. Herein we sought further develop our understanding confer sCJD using a systematic gene...
Syntaxin-6, a SNARE protein involved in intracellular trafficking, is proposed risk factor for sporadic prion disease, progressive supranuclear palsy and Alzheimer's disease. However, no study has validated its functional role these diseases, explored the disease stage at which it acting nor mechanism of action. Here, we show that syntaxin-6 acts early stages experimental mice by increasing transmission following inoculation with low doses. Conversely, does not affect propagation kinetics or...
Abstract Centrosome amplification (CA) is highly prevalent in cancer. It strongly associated with tumor progression and worse prognosis a variety of different cancers. Preclinical studies have demonstrated that CA can trigger initiation as well cancer cell invasion. Thus, known to be promising therapeutic target. We previously identified Transforming Acidic Coiled-Coil Containing Protein 3 (TACC3) being overexpressed tumors CA. TACC3 forms distinct functional interactomes regulating spindle...
Sporadic Creutzfeldt-Jakob disease (sCJD), the most common human prion disease, is thought to occur when cellular protein (PrPC) spontaneously misfolds and assembles into fibrils, culminating in fatal neurodegeneration. In a genome-wide association study of sCJD, we recently identified risk variants around gene STX6, with evidence suggest causal increase STX6 expression disease-relevant brain regions. encodes syntaxin-6, SNARE primarily involved early endosome trans-Golgi network retrograde...
<p>The purpose of this pilot study was to explore the approaches depression care preferred by older home-care patients and examine characteristics associated with those preferences. Twenty-eight long-term patients, ages 62 95, were interviewed. Patients ranked their preferences provided rationale for responses. Results indicated prayer highest percentage (50%). Comparing without experience, latter group. The results highlight importance addressing patient during planning improve...
Human prion diseases are rare, transmissible and often rapidly progressive dementias. The most common type, sporadic Creutzfeldt-Jakob disease (sCJD), is highly variable in clinical duration age at onset. Genetic determinants of late onset or slower progression might suggest new targets for research therapeutics. We assembled array genotyped sCJD cases diagnosed life autopsy. Clinical (median:4, interquartile range (IQR):2.5–9 (months)) was available 3,773 (median:67, IQR:61–73 (years))...
Abstract Sporadic Creutzfeldt-Jakob disease (sCJD), the most common human prion disease, is thought to occur when cellular protein (PrP C ) spontaneously misfolds and assembles into fibrils, culminating in fatal neurodegeneration. In a genome-wide association study of sCJD, we recently identified risk variants around gene STX6 , with evidence suggest causal increase expression disease-relevant brain regions. encodes syntaxin-6, SNARE primarily involved early endosome trans -Golgi network...
Abstract Prions replicate via the autocatalytic conversion of cellular prion protein (PrPC) into fibrillar assemblies misfolded PrP. While this process has been extensively studied in vivo and vitro, non-physiological reaction conditions fibril formation vitro have precluded identification mechanistic analysis proteins, which may alter PrP self-assembly replication. Here, we developed a assay for recombinant murine human (23-231) under near-native (NAA) to study effect be risk factors or...
The High Mobility Group (HMG) chromosomal proteins have been implicated as structural of transcriptionally poised chromatin in animal systems. Despite the suspected functions these proteins, no bioassay for them exists and they are defined operationally (by procedures used to isolate purify them). Plant systems that can be HMG proteins. However, because lack suitable bioassays plant structurally distinct from their putative counterparts, clear relationship between has established. One...
Abstract Prions are assemblies of misfolded prion protein that cause several fatal and transmissible neurodegenerative diseases, with the most common phenotype in humans being sporadic Creutzfeldt-Jakob disease (sCJD). Aside from variation itself, molecular risk factors not well understood. Prion prion-like mechanisms thought to underpin disorders meaning elucidation could have broad relevance. Herein we sought further develop our understanding confer sCJD using a systematic gene...
Abstract Human prion diseases are rare, transmissible and often rapidly progressive dementias. The most common type, sporadic Creutzfeldt-Jakob disease (sCJD), is highly variable in clinical duration age at onset. Genetic determinants of late onset or slower progression might suggest new targets for research therapeutics. We assembled array genotyped sCJD cases diagnosed life autopsy. Clinical (median:4, interquartile range (IQR):2.5-9 (months)) was available 3,773 (median:67, IQR:61-73...
This scientific commentary refers to ‘Inhibition of insulin-degrading enzyme in human neurons promotes amyloid-β deposition’ by Rowland et al. (https://doi.org/10.1042/NS20230016). Insulin-degrading (IDE) and neprilysin (NEP) have been proposed as two Aβ-degrading enzymes supported genetics vivo data. provide complementary evidence a key role for IDE Aβ metabolism induced pluripotent stem cell (iPSC)-derived cortical neurons.