Department: Pathobiology and Population Sciences

Campus: Hawkshead

Research Groups: Host-Pathogen Interactions and Vaccinology

Clive is a Lecturer for the PPS department at the Royal Veterinary College. Clive’s primary research interest is in neurodegenerative diseases, specifically those caused following protein misfolding. He also has interests in membrane biology, glycosylphosphatidylinositols, membrane rafts and cell signalling.

Clive completed a PhD from University College London on the pathology of Malaria in 1991. He investigated the theory that cerebral malaria was due to a hyperactivity of the hosts’ immune system resulting in a “cytokine storm”.

From 1991 until the end of 1998 Clive worked at the Institute of Molecular Medicine in Oxford and the MRC unit, Fajara, The Gambia. From 1999 he joined Professor Alun Williams, first at Glasgow University Veterinary School and later moved to the RVC at the beginning of 2005 where he took his current post.

Clive’s primary research interest is in neurodegenerative diseases, specifically those caused following protein misfolding (such as prion, Alzheimer’s and Parkinson’s diseases). Clive’s research encompasses 3 main themes. (1) The formation of prions within neuronal cells and how their formation can be blocked. (2) How the accumulation of misfolded proteins (either prions or the Aβ1-42 peptide that is thought to intiate pathogenesis in Alzheimer’s disease) causes damage to synapses (synaptotoxity) and ultimately neuronal death. The synapse damage represents the early stage of neurodegenerative disease. Clive’s research is aimed at stopping the synaptic destruction, and allowing the growth of synaptic connections. (3) The role of neuroinflammation, the responses of immune cells within the brain to cell damage, that occurs with Alzheimer’s and prion diseases.

Underlying these research interests is the concept that membrane biology and abnormal cell signaling pathways are important in the development of these diseases. Clive is particularly interested in the role of cholesterol in cell membranes and its effect specific “lipid raft” micro-domains, on cell signaling (phospholipase A2) and intracellular trafficking. These studies have identified a number of novel drugs that may be able to retard the progression of prion and Alzheimer’s disease.

Osborne C, West E, & Bate C. (2018)

The phospholipase A2 pathway controls a synaptic cholesterol ester cycle and synapse damage.

Journal of Cell Science 131 (8), doi: 10.1242/jcs.211789.

 

Bate, C; Williams, A. (2018)
Monomeric amyloid-beta reduced amyloid-beta oligomer-induced synapse damage in neuronal cultures.
Neurobiology of Disease 11148-58.

McHale-Owen, H; Bate, C. (2018)
Cholesterol ester hydrolase inhibitors reduce the production of synaptotoxic amyloid-beta oligomers.
Biochimica et Biophysica Acta-Molecular Basis of Disease, 1864;3:649-659.

Williams, R S B; Bate, C. (2017)
Valproic acid and its congener propylisopropylacetic acid reduced the amount of soluble amyloid-β oligomers released from 7PA2 cells.
Neuropharmacology,  12854-62.

West, E; Osborne, C; Bate, C. (2017)
The cholesterol ester cycle regulates signalling complexes and synapse damage caused by amyloid-β.
Journal of Cell Science, 1303050-3059.
 

Bate, C. (2017)
Can we switch production of toxic Aβ oligomers to neuroprotective Aβ monomers to allow synapse regeneration?.
Neural Regeneration Research, 12;9:1437-1438.
 

Bate, C. (2017)
Breaking the Cycle, Cholesterol Cycling, and Synapse Damage in Response to Amyloid-β.
Journal of Experimental Neuroscience, 11.
 

Nolan, W; McHale-Owen, H; Williams, A. (2017)
Sialylated glycosylphosphatidylinositols suppress the production of toxic amyloid-β oligomers.
Journal of Biological Chemistry,  474;17:3045-3058.
 

Osborne, C; West, E; Nolan, W; McHale-Owen, H; Williams, A; Bate, C. (2016)
Glimepiride protects neurons against amyloid-beta-induced synapse damage.
NEUROPHARMACOLOGY, 101225-236.
 

Williams, R S B; Bate, C. (2016)
An in vitro model for synaptic loss in neurodegenerative diseases suggests a neuroprotective role for valproic acid via inhibition of cPLA(2) dependent signalling.
NEUROPHARMACOLOGY, 101566-575.

Bate, C; Nolan, W; Williams, A. (2016)
Glycosylphosphatidylinositols: More than just an anchor?
Communicative & Integrative Biology, 9;2:e1149671-e1149671.
 

Bate, C; Nolan, W; Williams, A. (2016)
Does the tail wag the dog? How the structure of a glycosylphosphatidylinositol anchor affects prion formation.
Prion, 10;2:127-30.

Bate, C; Williams, A. (2015)
α-Synuclein-Induced Synapse Damage in Cultured Neurons Is Mediated by Cholesterol-Sensitive Activation of Cytoplasmic Phospholipase A2.
Biomolecules, 5;1:178-93.
 

Bate, C. (2015)
Enhanced neuronal degradation of amyloid-beta oligomers allows synapse regeneration.
NEURAL REGENERATION RESEARCH, 10;5:700-701.
 

Simmons C, Ingham V, Williams A & Bate C. (2014) - Platelet-activating factor antagonists increase the removal of amyloid-β42 from neurons via regulation of cholesterol ester hydrolases. Alzheimer’s Research & Therapy 6:15.

Ingham V, Williams A & Bate C (2014) Glimepiride reduces CD14 expression and cytokine production from macrophages Journal of Neuroinflammation 11:115.
 

Bate C & Williams A. (2012) Neurodegeneration is induced by the clustering of sialic acid-containing glycosylphosphatidylinositol anchors of prion proteins. The Journal of Biological Chemistry in press

Bate C & Williams A. (2011) Amyloid-β-induced synapse damage is mediated via cross-linkage of cellular prion proteins. The Journal of Biological Chemistry 286, 37955 - 37963.

Bate C & Williams A. (2011) Ethanol protects cultured neurons against amyloid-β and α-synuclein-induced synapse damage. Neuropharmacology 61, 1406 - 1412.

Bate C & Williams A. (2011) PrPC with a monoacylated glycosylphosphatidylinositol anchor modifies cell membranes, inhibits cell signalling and reduces prion formation – Prion 5 (2) 65 - 68.

Bate C & Williams A (2011) Monoacylated cellular prion protein modifies cell membranes, inhibits cell signaling and reduces prion formation. The Journal of Biological Chemistry 286. 8752 - 8758.

Bate C, Ingham V & Williams A. (2011) Inhibition of phospholipase A2 increased the removal of the prion derived peptide PrP82-146 from cultured neurons. Neuropharmacology 60. 365 – 372.

Bate C, Gentleman S & Williams A. (2010) α-synuclein induced synapse damage is enhanced by Aβ1-42 Molecular Neurodegeneration 5. 55 (December).
 

Bate C, Tayebi M & Williams A. (2010) A glycosylphosphatidylinositol analogue reduced prion derived peptide mediated activation of cytoplasmic phospholipase A2, synapse degeneration and neuronal death Neuropharmacology 59, 93-99.

Bate C, Tayebi M & Williams A. (2010) Glycosylphosphatidylinositol anchor analogues sequester cholesterol and reduce prion formation Journal of Biological Chemistry 285, 22017 - 22026.

Bate C, Tayebi M & Williams A. (2010) Phospholipase A2 inhibitors protect against prion and Aβ mediated synapse degeneration Molecular Neurodegeneration, 5:13.

Bate C, Tayebi M & Williams A. (2010) The glycosylphosphatidylinositol anchor is a major determinant of prion binding and infectivity. Biochemistry J 428 (1) 95-101.

Bate C, Tayebi M, Diomede L, Salmona M & Williams A. (2010) Polyunsaturated fatty acids reduce prion-mediated synapse damage in vitro. Neurotoxicity Research, 17 (3) 203-214.

Bate C, Tayebi M, Diomede L, Salmona M & Williams. A. (2008) Docosahexaenoic and eicosapentaenoic acids increase prion formation in neuronal cells. BMC Biology, 6. 139 (September).

Bate C, Tayebi M, Diomede L, Salmona M & Williams A. (2009) Glimepiride reduced the expression of PrPC, prevents PrPSc formation and protects against prion-mediated neurotoxicity PLoSONE 4 (12) e8221.

Bate C & Williams A. (2008) Do prion-induced changes in cholesterol trigger neurodegeneration? Future Neurology 3 (4) 367-370.

BATE, C., TAYEBI, M. & WILLIAMS, A. (2008) Ginkgolides protect against amyloid-beta1-42-mediated synapse damage in vitro. Mol Neurodegener 3, 1. PubMed ID 18179689

BATE, C., TAYEBI, M. & WILLIAMS, A. (2008) Sequestration of free cholesterol in cell membranes by prions correlates with cytoplasmic phospholipase A2 activation. BMC Biol 6, 8. PubMed ID 18269734

BATE, C., TAYEBI, M. & WILLIAMS, A. (2008) Cholesterol esterification reduces the neurotoxicity of prions. Neuropharmacology 54, 1247-1253. PubMed ID 18448139

BATE, C., MARSHALL, V., COLOMBO, L., DIOMEDE, L., SALMONA, M. & WILLIAMS, A. (2008) Docosahexaenoic and eicosapentaenoic acids increase neuronal death in response to HuPrP82-146 and Abeta 1-42. Neuropharmacology 54, 934-943. PubMed ID 18355880

WILSON, R., BATE, C., BOSHUIZEN, R., WILLIAMS, A. & BREWER, J. (2007) Squalestatin alters the intracellular trafficking of a neurotoxic prion peptide. BMC Neurosci 8, 99. PubMed ID 18034899

TAYEBI, M., BATE, C., HAWKE, S. & WILLIAMS, A. (2007) A role for B lymphocytes in anti-infective prion therapies? Expert Rev Anti Infect Ther 5, 631-638. PubMed ID 17678426

KEMPSTER, S., BATE, C. & WILLIAMS, A. (2007) Simvastatin treatment prolongs the survival of scrapie-infected mice. Neuroreport 18, 479-482. PubMed ID 17496807

BATE, C. & WILLIAMS, A. (2007) Squalestatin protects neurons and reduces the activation of cytoplasmic phospholipase A2 by Abeta(1-42). Neuropharmacology 53, 222-231. PubMed ID 17583757

BATE, C., RUMBOLD, L. & WILLIAMS, A. (2007) Cholesterol synthesis inhibitors protect against platelet-activating factor-induced neuronal damage. J Neuroinflammation 4, 5. PubMed ID 17233902

BATE, C., KEMPSTER, S. & WILLIAMS, A. (2006) Prostaglandin D2 mediates neuronal damage by amyloid-beta or prions which activates microglial cells. Neuropharmacology 50, 229-237. PubMed ID 16289250

BATE, C., KEMPSTER, S. & WILLIAMS, A. (2006) Platelet-activating factor antagonists protect amyloid-beta damaged neurons from microglia-mediated death. Neuropharmacology 51, 173-181. PubMed ID 16678220

BATE, C., KEMPSTER, S., LAST, V. & WILLIAMS, A. (2006) Interferon-gamma increases neuronal death in response to amyloid-beta1-42. J Neuroinflammation 3, 7. PubMed ID 16569229

BATE, C., BOSHUIZEN, R. & WILLIAMS, A. (2005) Microglial cells kill prion-damaged neurons in vitro by a CD14-dependent process. J Neuroimmunol 170, 62-70. PubMed ID 16225933

BATE, C. & WILLIAMS, A. (2004) Role of glycosylphosphatidylinositols in the activation of phospholipase A2 and the neurotoxicity of prions. J Gen Virol 85, 3797-3804. PubMed ID 15557253

BATE, C. & WILLIAMS, A. (2004) Detoxified lipopolysaccharide reduces microglial cell killing of prion-infected neurons. Neuroreport 15, 2765-2768. PubMed ID 15597050

BATE, C., VEERHUIS, R., EIKELENBOOM, P. & WILLIAMS, A. (2004) Microglia kill amyloid-beta1-42 damaged neurons by a CD14-dependent process. Neuroreport 15, 1427-1430. PubMed ID 15194867

BATE, C., SALMONA, M. & WILLIAMS, A. (2004) The role of platelet activating factor in prion and amyloid-beta neurotoxicity. Neuroreport 15, 509-513. PubMed ID 15094513

BATE, C., SALMONA, M. & WILLIAMS, A. (2004) Ginkgolide B inhibits the neurotoxicity of prions or amyloid-beta1-42. J Neuroinflammation 1, 4. PubMed ID 15285798

BATE, C., SALMONA, M., DIOMEDE, L. & WILLIAMS, A. (2004) Squalestatin cures prion-infected neurons and protects against prion neurotoxicity. J Biol Chem 279, 14983-14990. PubMed ID 14754889

BATE, C., REID, S. & WILLIAMS, A. (2004) Phospholipase A2 inhibitors or platelet-activating factor antagonists prevent prion replication. J Biol Chem 279, 36405-36411. PubMed ID 15210691

BATE, C., VEERHUIS, R., EIKELENBOOM, P. & WILLIAMS, A. (2003) Neurones treated with cyclo-oxygenase-1 inhibitors are resistant to amyloid-beta1-42. Neuroreport 14, 2099-2103. PubMed ID 14600505

BARRET, A., TAGLIAVINI, F., FORLONI, G., BATE, C., SALMONA, M., COLOMBO, L., DE LUIGI, A., LIMIDO, L., SUARDI, S., ROSSI, G., AUVRE, F., ADJOU, K. T., SALES, N., WILLIAMS, A., LASMEZAS, C. & DESLYS, J. P. (2003) Evaluation of quinacrine treatment for prion diseases. J Virol 77, 8462-8469. PubMed ID 12857915

EIKELENBOOM, P., BATE, C., VAN GOOL, W. A., HOOZEMANS, J. J., ROZEMULLER, J. M., VEERHUIS, R. & WILLIAMS, A. (2002) Neuroinflammation in Alzheimer's disease and prion disease. Glia 40, 232-239. PubMed ID 12379910

BATE, C., RUTHERFORD, S., GRAVENOR, M., REID, S. & WILLIAMS, A. (2002) Cyclo-oxygenase inhibitors protect against prion-induced neurotoxicity in vitro. Neuroreport 13, 1933-1938. PubMed ID 12395095

BATE, C., REID, S. & WILLIAMS, A. (2001) Killing of prion-damaged neurones by microglia. Neuroreport 12, 2589-2594. PubMed ID 11496154

Clive lectures on prion and Alzheimer’s diseases to the BSc Bioveterinary Science course. He also lectures on basic immunology and parasitology, specifically how a parasite is successful and mechanisms of immune system evasion. He has also assisted with the BVetMed course and the Control of Infectious Disease MSc.

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