A5068422877- Mitochondrial Function and Pathology
- Amino Acid Enzymes and Metabolism
- Metabolism and Genetic Disorders
- Autophagy in Disease and Therapy
- Tryptophan and brain disorders
- Cytokine Signaling Pathways and Interactions
- Monoclonal and Polyclonal Antibodies Research
- interferon and immune responses
- Cellular transport and secretion
- Enzyme Structure and Function
- Ion channel regulation and function
- Synthesis and Biological Evaluation
- Lysosomal Storage Disorders Research
- Alzheimer's disease research and treatments
- Chemical Reactions and Mechanisms
- Trypanosoma species research and implications
- ATP Synthase and ATPases Research
- Parkinson's Disease Mechanisms and Treatments
- Coenzyme Q10 studies and effects
- Peroxisome Proliferator-Activated Receptors
- Neuroinflammation and Neurodegeneration Mechanisms
- T-cell and B-cell Immunology
- Synthesis and Characterization of Heterocyclic Compounds
- Protein purification and stability
- Immune Response and Inflammation
MRC Protein Phosphorylation and Ubiquitylation Unit
2013-2020
University of Dundee
2013-2020
Royal Derby Hospital
2018
University of Nottingham
2018
Royal Devon & Exeter NHS Foundation Trust
2017
Medical Research Council
1975-2016
University College London
2009-2013
Instituto Superior Técnico
2013
National Hospital for Neurology and Neurosurgery
2009-2012
Hospital Kuala Lumpur
2010
In this study, we develop a simple assay to identify mitophagy inducers on the basis of use fluorescently tagged mitochondria that undergo colour change lysosomal delivery. Using assay, iron chelators as family compounds generate strong response. Iron chelation‐induced requires cells glycolysis, but does not require PINK1 stabilization or Parkin activation, and occurs in primary human fibroblasts well those isolated from Parkinson's patient with mutations. Thus, have identified characterized...
Autophagic turnover of mitochondria, termed mitophagy, is proposed to be an essential quality-control (QC) mechanism pathophysiological relevance in mammals. However, if and how mitophagy proceeds within specific cellular subtypes vivo remains unclear, largely because a lack tractable tools models. To address this, we have developed "mito-QC," transgenic mouse with pH-sensitive fluorescent mitochondrial signal. This allows the assessment architecture vivo. Using confocal microscopy,...
Unlike most other cell types, neurons preferentially metabolize glucose via the pentose phosphate pathway (PPP) to maintain their antioxidant status.Inhibiting PPP in neuronal models causes death.In rodents, inhibition of this selective dopaminergic death leading motor deficits resembling parkinsonism.Using postmortem human brain tissue, we characterized metabolism sporadic Parkinson's disease (PD), Alzheimer's (AD), and controls.AD brains showed increased nicotinamide adenine dinucleotide...
<b>Objective:</b> To describe the current treatment; clinical, biochemical, and molecular findings; clinical follow-up of patients with aromatic l-amino acid decarboxylase (AADC) deficiency. <b>Method:</b> Clinical biochemical data 78 AADC deficiency were tabulated in a database pediatric neurotransmitter disorders (JAKE). A total 46 have been previously reported; 32 are described for first time. <b>Results:</b> In 96% AADC-deficient patients, symptoms (hypotonia 95%, oculogyric crises 86%,...
Article2 July 2015Open Access Source Data mTOR activates the VPS34–UVRAG complex to regulate autolysosomal tubulation and cell survival Michael J Munson MRC Protein Phosphorylation Ubiquitylation Unit, College of Life Sciences, University Dundee, UK Search for more papers by this author George FG Allen Rachel Toth David G Campbell John M Lucocq School Medicine, St Andrews, Ian Ganley Corresponding Author Information Munson1, Allen1, Toth1, Campbell1, Lucocq2 1 1MRC 2School *Corresponding...
The isolation and characterization of the soluble peptides from CNBr digest calcium ion-transporting adenosine triphosphatase protein rabbit skeletal sarcoplasmic reticulum are described. 562 unique residues were placed in sequences. remaining part (about 500 residues) yielded long hydrophobic sequences that contained all but one tryptophan probably derived largely intramembranous parts protein. Three stretches primary structure, constituting half protein, have been reconstructed information...
HIF1α-dependent mitophagy facilitates cardiomyoblast differentiation – Mitophagy is thought to play a key role in eliminating damaged mitochondria, with diseases such as cancer and neurodegeneration exhibiting defects this process. also involved cell maturation, potentially through modulating mitochondrial metabolic reprogramming. Here we examined that induced upon iron chelation found the transcriptional activity of HIF1α, part upregulation BNIP3 NIX, an essential mediator pathway SH-SY5Y...
SUMMARY Highly purified interferon-α (IFN-α) prepared from a human lymphoblastoid line (Namalwa) was analysed by gel filtration and polyacrylamide electrophoresis (PAGE). Gel separated the IFN-a into two peaks (A B). All compo- nents of peak A were retained monoclonal antibody (NK2) column, but some those B not retained. The IFN that bound active on mouse cells could be resolved major bands PAGE. fraction (about 75% interferon protein) means although complete purification crude achieved in...
The study examined how the mitochondrial enzyme monoamine oxidase-A (MAO-A), which produces hydrogen peroxide as a catalytic by-product, influences death and survival mechanisms. Targeted microRNA (miRNA) was used to stably knock down MAO-A mRNA, protein, activity by 60-70% in SH-SY5Y human neuroblastoma cells. effects of knockdown (KD) on ATP, oxidative stress, electron transport chain, following exposure toxins were assessed. In control cells, complex I inhibition resulted caspase-mediated...
Abstract When Escherichia coli 30 S ribosomal subunits are reacted with protein-protein bifunctional reagents, a number of protein pairs as well aggregates containing three or more proteins formed. In the present study we have purified one obtained by reaction either radioactive nonradioactive dimethylsuberimidate. Following molecular weight determination and ammonolysis, pair was shown to consist S5 S8. The native structure complex surmised from its capacity be reconstituted into...
J. Neurochem. (2010) 114 , 87–96. Abstract Pyridoxal 5′‐phosphate, the active form of vitamin B 6 is an essential cofactor for multiple enzymes, including aromatic l ‐amino acid decarboxylase that catalyses final stage in production neurotransmitters dopamine and serotonin. In two patients with inherited disorders metabolism, we observed reductions plasma activity. one patient, this change was related to increase K m pyridoxal 5′‐phosphate. Furthermore, 5′‐phosphate‐deficient human SH‐SY5Y...
The isolation and the determination of amino-acid sequences soluble tryptic peptides, derived by cleavage at arginine residues, succinylated (3-carboxypropionylated) S-carboxymethylated adenosine triphosphatase protein rabbit skeletal sarcoplasmic reticulum are described. Treatment with succinic anhydride gave a derivative that was readily digested trypsin, yielding two distinct sets peptides. One set comprises large, relatively hydrophobic, peptides highly aggregated (or insoluble) in...
The locations of the six disulphide bonds and single free cysteine residue in a variant surface glycoprotein, VSG 117, from African trypanosome Trypanosoma brucei have been determined to be Cys-14--Cys-140, Cys-121--Cys-182, Cys-389--Cys-404, Cys-398--417, Cys-447--Cys-461 Cys-455--Cys-468. Cys-244 bears thiol group, which is unreactive towards 2-nitro-5-thiocyanobenzoate native molecule probably buried. Biosynthetically incorporated [35S]cysteine aided location bonds. Two...
The soluble peptides from the peptic digest of reduced S-carboxymethylated 3-carboxypropionylated adenosine triphosphatase protein have been isolated and most their structures determined. About 397 residues were represented in these peptides. was digested with thermolysin, containing arginine or carboxymethylcysteine characterized. Some tryptic staphylococcal-proteinase digests are described. information contained within has used to reconstruct long stretches sequence ATPase that constitute...
The binding of NAD+ to glyceraldehyde 3-phosphate dehydrogenase (EC 1.2.1.12) from Bacillus stearothermophilus has been studied by measurement protein fluorescence quenching. Slight negative co-operativity was observed in the third and fourth coenzyme molecules tetrameric enzyme. first two were tightly bound. In this respect enzyme resembles that sturgeon muscle rather than yeast.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Mitomycin Antibiotics. Synthetic Studies. XXII. Antibacterial Structure-Activity Relationships in the Indoloquinone SeriesMartin Weiss, Gunnar Redin, George Allen, Albert Dornbush, Harry Lindsay, John Poletto, William Remers, Reta Roth, and Adolf SlobadaCite this: J. Med. Chem. 1968, 11, 4, 742–745Publication Date (Print):July 1, 1968Publication History Published online26 November 2002Published inissue 1 July...
Repetitive excessive alcohol intoxication leads to neuronal damage and brain shrinkage. We examined cytoskeletal protein expression in human post-mortem tissue from Brodmann’s area 9 of the prefrontal cortex (PFC). Brain samples 44 individuals were divided into equal groups 11 control, alcoholic, non-alcoholic suicides, suicide alcoholics matched for age, sex, delay. Tissue alcoholic cohorts displayed significantly reduced α- β-tubulins, increased levels acetylated α-tubulin. Protein histone...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSolvents of Low Nucleophilicity. III. The Effect Remote Substituents in the Addition Trifluoroacetic Acid to Substituted AlkenesPaul E. Peterson and George. AllenCite this: J. Am. Chem. Soc. 1963, 85, 22, 3608–3613Publication Date (Print):November 1, 1963Publication History Published online1 May 2002Published inissue 1 November 1963https://pubs.acs.org/doi/10.1021/ja00905a017https://doi.org/10.1021/ja00905a017research-articleACS PublicationsRequest...