A5020554752- Alzheimer's disease research and treatments
- Parkinson's Disease Mechanisms and Treatments
- Prion Diseases and Protein Misfolding
- Cholinesterase and Neurodegenerative Diseases
- Computational Drug Discovery Methods
- Supramolecular Self-Assembly in Materials
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Dementia and Cognitive Impairment Research
- Neurological disorders and treatments
- Neurological diseases and metabolism
- Amyotrophic Lateral Sclerosis Research
- S100 Proteins and Annexins
- Peptidase Inhibition and Analysis
- Biochemical effects in animals
- Protein Structure and Dynamics
- Neuroinflammation and Neurodegeneration Mechanisms
- Cannabis and Cannabinoid Research
- Trace Elements in Health
- 14-3-3 protein interactions
- Spectroscopy Techniques in Biomedical and Chemical Research
- Nuclear Receptors and Signaling
- Cerebrovascular and genetic disorders
- Cellular transport and secretion
- Lipid Membrane Structure and Behavior
- Spectroscopy and Chemometric Analyses
Lancaster University
2014-2024
Kyoto Prefectural University of Medicine
2020
National Institutes for Quantum Science and Technology
2020
The University of Sydney
2006-2019
Health & Life (Taiwan)
2018
Furness College
2018
Google (United States)
2017
Sax Institute
2016
University of Nottingham
1983-2015
Queen's Medical Centre
1983-2015
Biologically formed nanoparticles of the strongly magnetic mineral, magnetite, were first detected in human brain over 20 y ago [Kirschvink JL, Kobayashi-Kirschvink A, Woodford BJ (1992) Proc Natl Acad Sci USA 89(16):7683-7687]. Magnetite can have potentially large impacts on due to its unique combination redox activity, surface charge, and behavior. We used analyses electron microscopy identify abundant presence magnetite that are consistent with high-temperature formation, suggesting,...
To date there is no accepted clinical diagnostic test for Parkinson's disease (PD) based on biochemical analysis of blood or cerebrospinal fluid (CSF). alpha-Synuclein (alpha-syn) protein has been linked to the pathogenesis PD with discovery mutations in gene encoding alpha-syn familial cases early-onset PD. Lewy bodies and neurites, which constitute main pathological features brains patients sporadic dementia bodies, are formed by conversion soluble monomers into insoluble aggregates. We...
Parkinson's disease (PD) and other related disorders are characterized by the accumulation of fibrillar aggregates alpha-synuclein protein (alpha-syn) inside brain cells. It is likely that formation alpha-syn plays a seminal role in pathogenesis at least some these diseases, because two different mutations gene encoding have been found inherited forms PD. alpha-Syn mainly expressed neuronal cells generally considered to exist as cytoplasmic protein. Here, we report unexpected identification...
The repeated head trauma experienced by boxers can lead to the development of dementia pugilistica (DP)--punch drunk syndrome. neuropathology DP in a classic report Corsellis et al describes presence numerous neurofibrillary tangles absence plaques, contrast profusion and plaques seen Alzheimer's disease (AD). cases used that were re-investigated with immunocytochemical methods an antibody raised beta-protein present AD plaques. We found all substantial tangle formation showed evidence...
There is accumulating evidence that soluble amyloid-beta (Abeta) oligomers, rather than amyloid fibrils, are the principal pathogenic species in Alzheimer disease (AD). Here, we have developed a novel enzyme-linked immunosorbent assay (ELISA) specific for high-molecular-weight (HMW) Abeta oligomers. Analysis of oligomers derived from synthetic 1-42, by size-exclusion chromatography (SEC), revealed our ELISA specifically detected HMW 40-200 kDa. Using this ELISA, significantly higher...
There is still a substantial unmet need for less invasive and lower-cost blood-based biomarkers to detect brain Alzheimer's disease (AD) pathology. This study aimed determine whether quantification of plasma tau phosphorylated at threonine 181 (p-tau181) informative in the diagnosis AD. We have developed novel ultrasensitive immunoassay quantify p-tau181, measured levels p-tau181 three cohorts. In first cohort composed 20 AD patients 15 age-matched controls, were significantly higher than...
Alzheimer disease and familial British dementia are neurodegenerative diseases that characterized by the presence of numerous amyloid plaques in brain. These lesions contain fibrillar deposits beta-amyloid peptide (Abeta) (ABri), respectively. Both peptides toxic to cells culture, there is increasing evidence early "soluble oligomers" entity rather than mature fibrils. The molecular mechanisms responsible for this toxicity not clear, but case Abeta, one prominent hypothesis can induce...
A number of neurodegenerative diseases including Parkinson's disease, dementia with Lewy bodies (DLB) and multiple system atrophy are characterized by the formation intraneuronal accumulation fibrillar aggregates alpha-synuclein (alpha-syn) protein in affected brain regions. These other findings suggest that alpha-syn plays an important role pathogenesis these diseases. However, more recently it has been reported early amyloid or 'soluble oligomers' pathogenic species lead to...
Parkinson's disease (PD) is characterized by the presence of Lewy bodies containing phosphorylated and aggregated α-synuclein (α-syn). α-Syn present in human body fluids, including blood plasma, a potential biomarker for PD. Immunoassays total oligomeric forms both normal (at Ser-129) α-syn have been used to assay plasma samples from longitudinal cohort 32 patients with PD (sampled at mo 0, 1, 2, 3), as well single group 30 healthy control participants. The levels varied greatly between...
Convergent biochemical and genetic evidence suggests that the formation of alpha-synuclein (alpha-syn) protein deposits is an important and, probably, seminal step in development Parkinson's disease (PD), dementia with Lewy bodies (DLB) multiple system atrophy (MSA). It has been reported transgenic animals overexpressing human alpha-syn develop lesions similar to those found brain PD, together a progressive loss dopaminergic cells associated abnormalities motor function. Inhibiting and/or...
Abstract There have been no longitudinal studies on α-synuclein as a potential biomarker for the progression of Parkinson's disease (PD). Here, blood plasma ‘total α-synuclein’ and ‘Ser-129 phosphorylated were assayed at 4–6 monthly intervals from cohort 189 newly-diagnosed patients with PD. For log-transformed data, total levels increased time up to 20 yrs after appearance initial symptoms (p = 0.012), whereas remained constant over this same period. The mean level α-synuclein, but not was...
Convergent biochemical and genetic evidence suggests that the formation of β-amyloid (Aβ) deposits in brain is an important and, probably, seminal step development Alzheimer's disease (AD). Recent studies support hypothesis Aβ soluble oligomers are pathogenic species prompt disease. Inhibiting self-oligomerization could, therefore, provide a novel approach to treating underlying cause AD. Here, we designed potential peptide-based aggregation inhibitors containing amino acid sequences (KLVFF)...
Autopsy studies have shown that about 55% of patients with frontotemporal lobar degeneration (FTLD) and 25% Alzheimer's disease (AD) harbour TDP-43 immunoreactive pathological changes in their brains. Using ELISA, we investigated whether could detect the presence, or increased amounts, plasma FTLD AD compared to normal control subjects. We detected elevated levels protein 46% clinical dementia (FTD) 22% AD, 8% The proportions FTD showing raised correspond closely those known from autopsy...
The formation of β-amyloid (Aβ) deposits in the brain is likely to be a seminal step development Alzheimer's disease. Recent studies support hypothesis that Aβ soluble oligomers are toxic cells and have potent effects on memory learning. Inhibiting early stages aggregation could, therefore, provide novel approach treating underlying cause AD. We designed retro-inverso peptide (RI-OR2, H2N-r←G←k←l←v←f←f←G←r-Ac), based previously described inhibitor oligomer (OR2, H2N-R-G-K-L-V-F-F-G-R-NH2)....
Significance Vibrational spectroscopy is an ideal technique for analysis of biofluids, as it provides a “spectral fingerprint” all the molecules present within biological sample, thus generating holistic picture sample’s status. Neurodegenerative diseases lack early and accurate diagnosis, tests currently used their detection are either invasive or expensive time-consuming. This study blood plasma to diagnose differentiate various neurodegenerative diseases; achieved sensitivities...