Dr Nat Milton - Research

Dr Nat Milton's Research


Dr Nat Milton was trained in the parasitology, neuroendocrinology and clinical biochemistry areas, with his own research focussed on protein-protein interactions. Applying bioinformatics to drug discovery plus the development of diagnostic tools for use in disease settings such as neurodegenerative and endocrine diseases has been the major focus of his research. He discovered interactions between the Alzheimer's disease amyloid-ß peptide and the antioxidant enzyme catalase. He has also identified novel KiSS-1 derivatives, kissorphin's, that bind a number of amyloid proteins and have biological activity as neuropeptide-FF receptor agonists. The neuroprotective properties of endocannabinoids against amyloid-ß toxicity was probably his most important research discovery. He has applied the Bioinformatics techniques outlined on this website in a number of academic research and commercial studies. His recent focus has been on the application of bioinformatics to identify some of the human targets of the SARS-CoV-2 virus proteins.


Dr Nat Milton Online Research Profiles:


Leed Beckett University Profile: Dr Nat Milton

Google Scholar Profile:
Nathaniel Milton

ORCID Profile:
Dr Nathaniel G N Milton

ResearchGate Profile:
Nathaniel Milton

Dr Nat Milton Research Publications:


Yan, P., Zou, Z., Zhang, S., Wang, R., Niu, T., Zhang, X., Liu, D., Zhou, X., Chang, A.K., Milton, N.G.N, Jones, G.W., & He, J. (2021). Defining the mechanism of PDI interaction with disulfide-free amyloidogenic proteins: Implications for exogenous protein expression and neurodegenerative disease. Int. J. Biol. Macromol., 174, 175 - 184.

Cussell, P.J.G., Gomez Escalada, M., Milton, N.G.N. & Paterson, A.W.J. (2020) The N-formyl peptide receptors: contemporary roles in neuronal function and dysfunction. Neural Regen. Res., 15(7), 1191 - 1198.

Cussell, P.J.G., Howe, M.S., Illingworth, T.A., Gomez Escalada, M., Milton, N.G.N. & Paterson, A.W.J. (2019) The formyl peptide receptor agonist FPRa14 induces differentiation of Neuro2a mouse neuroblastoma cells into multiple distinct morphologies which can be specifically inhibited with FPR antagonists and FPR knockdown using siRNA. PLoS ONE, 14(6), e0217815.

Milton, N. (2017) Kissorphin peptides for use in the treatment of Alzheimer's disease, Creutzfeldt-Jakob disease or diabetes mellitus. United Kingdom Patent Publication Number GB2493313B.

Milton, N.G.N. & Harris, J.R. (2014) Chapter 23 - Polymorphism of Amyloid Fibrils and their Complexes with Catalase. In: Bio-nanoimaging: Protein Misfolding and Aggregation. Eds V.N. Uversky & Y.L. Lyubchenko, Academic Press, Boston, pp 255 - 262.

Chilumuri, A., Markiv, A. & Milton, N.G.N. (2014) Immunocytochemical staining of endogenous nuclear proteins with the HIS-1 anti-poly-histidine monoclonal antibody: a potential source of error in His-tagged protein detection. Acta Histochemica., 116(6), 1022 - 1028.

Chilumuri, A., Odell, M. & Milton, N.G.N. (2013) Benzothiazole aniline-tetra(ethylene glycol) and 3-amino-1,2,4-triazole inhibit neuroprotection against amyloid peptides by catalase overexpression in vitro. ACS Chem. Neurosci., 4(11), 1501 - 1512.

Chilumuri, A. & Milton, N.G.N. (2013) The role of neurotransmitters in protection against amyloid-β toxicity by KiSS-1 overexpression in SH-SY5Y neurons. ISRN Neurosci., 2013, 253210.

Chilumuri, A., Ashioti, M., Nercessian, A.N. & Milton, N.G.N. (2013) Immunolocalization of kisspeptin associated with amyloid-β deposits in the pons of an Alzheimer's disease patient. J. Neurodegen. Dis., 2013, 879710.

Milton, N.G.N. & Harris, J.R. (2013) Fibril formation and toxicity of the non-amyloidogenic rat amylin peptide. Micron, 44, 256 - 253.

Harris, J.R. & Milton, N.G.N. (2012) Introduction and technical survey: protein aggregation and fibrillogenesis. Subcell. Biochem., 65, 3 - 25.

Milton, N.G.N. (2012) In vitro activities of Kissorphin, a novel hexapeptide KiSS-1 derivative, in neuronal cells. J. Amino Acids, 2012, 691463.

Milton, N.G.N., Chilumuri, A., Rocha-Ferreira, E., Nercessian, A.N. & Ashioti, M. (2012) Kisspeptin prevention of amyloid-β peptide neurotoxicity in vitro. ACS Chem. Neurosci., 3(9), 706 - 719.

Milton, N. (2011) Kissorphin peptides for use in the treatment of Alzheimer's disease, Creutzfeldt-Jakob disease or diabetes mellitus. International Patent Application Publication Number WO 2011/144714 (A1).

Milton, N. (2011) Kisspeptin peptides for use in the treatment of Alzheimer's disease, Creutzfeldt-Jakob disease or diabetes mellitus. European Patent Application Publication Number EP2388012 (A1).

Harris, J.R. & Milton, N.G.N. (2010) Cholesterol in Alzheimer's disease and other amyloidogenic disorders. Subcell. Biochem., 51, 47 - 75.

Milton, N.G.N. & Harris, J.R. (2010) Human islet amyloid polypeptide fibril binding to catalase: a transmission electron microscopy and microplate study. ScientificWorldJournal, 10, 879 - 893.

Milton, N.G.N. & Harris, J.R. (2009) Polymorphism of Amyloid-β fibrils and its effects on Human Erythrocyte Catalase binding. Micron, 40, 800 - 810.

Milton, N.G.N. (2008) Homocysteine inhibits hydrogen peroxide breakdown by Catalase. Open Enzym. Inhib. J., 1, 34 - 41.

Milton, N.G.N. (2006) Protocols 6.39 Antiā€sense peptides. In Cell Biology Protocols, Eds D. Rickwood, J. Graham & J.R. Harris, Wiley, London, pp 353 - 358.

Milton, N.G.N. (2006) Protocols 6.40 Interactions between amyloid-β and enzymes. In Cell Biology Protocols, Eds D. Rickwood, J. Graham & J.R. Harris, Wiley, London pp 359 - 363.

Milton, N.G.N. (2006) Protocols 6.41 Amyloid-β phosphorylation. In Cell Biology Protocols, Eds D. Rickwood, J. Graham & J.R. Harris, Wiley, London pp 364 - 368.

Milton, N.G.N. (2005) Phosphorylated amyloid-β: the toxic intermediate in Alzheimer's disease neurodegeneration. Subcell. Biochem., 38, 381 - 402.

Milton, N.G.N. (2005) Phosphorylated Amyloid-beta 1-43 protein and its use in the treatment of Alzheimer's disease. European Patent Application Publication Number EP1538163.

Milton, N.G.N. (2004) Peptides for use in the treatment of Alzheimer's disease. United States Patent Application Publication Number US 2004/0072753.

Milton, N.G.N. (2004) Role of hydrogen peroxide in the aetiology of Alzheimer's Disease: implications for treatment. Drugs Aging 21(2), 81 - 100.

Vincent, I., Nagy, Z., Neve, R., Herrup, K., Milton, N., Smith, M., Wolozin, B., Chen, Y., Lu, K.P., Kinoshita, J., Strobel, G., Hallows, J., Bowser, R., Feinstein, D., Atwood, C., and Maiese, K. (2003) Transcript of Live Discussion: The Cell Cycle in Alzheimer's Disease: Let's Unite Around Division. J. Alzheimer’s Dis., 5, 251 - 262.

Milton, N.G.N. (2003) Peptides for use in the treatment of Alzheimer's disease. European Patent Application Publication Number EP1363939.

Milton, N.G.N. (2002) Anandamide and noladin ether prevent neurotoxicity of the human amyloid-β peptide. Neurosci. Lett., 332(2), 127 - 130.

Milton, N.G.N. (2002) The amyloid-β peptide binds to cyclin B1 and increases human cyclin-dependent kinase-1 activity. Neurosci. Lett., 322(2), 131 - 133.

Milton, N.G.N. (2002) Peptides for use in the treatment of Alzheimer's disease. International Patent Application Publication Number WO 02/36614.

Byrne, D.J., Jagroop, I.A., Montgomery, H.E., Thomas, M., Mikhailidis, D.P., Milton, N.G., & Winder, A.F. (2002) Lipoprotein (a) does not participate in the acute phase response to training or extreme physical activity and is unlikely to enhance any associated immediate cardiovascular risk. J. Clin. Pathol., 55(4), 280 - 285.

Milton, N.G.N. (2001) Inhibition of catalase activity with 3-amino-triazole enhances the cytotoxicity of the Alzheimer’s amyloid-β peptide. Neurotoxicology, 22(6), 767 - 74.

Milton, N.G.N. (2001) Phosphorylation of amyloid-β at the serine 26 residue by human cdc2 kinase. Neuroreport, 12(17), 3839 - 3844.

Milton, N.G.N., Mayor, N.P. & Rawlinson, J. (2001) Identification of amyloid-β binding sites using an antisense peptide approach. Neuroreport, 12(11), 2561 - 2566.

Milton, N.G.N. (1999) Amyloid-β binds catalase with high affinity and inhibits hydrogen peroxide breakdown. Biochem. J., 344(2), 293 - 296.

Milton, N.G.N., Bessis, A., Changeux, J-P. & Latchman, D.S. (1996) Differential regulation of neuronal nicotinic acetylcholine receptor subunit gene promoters by Brn-3 POU family transcription factors. Biochem. J., 317(2), 419 - 423.

Milton, N.G.N., Bessis, A., Changeux, J-P. & Latchman, D.S. (1995) The neuronal nicotinic acetylcholine receptor alpha2 subunit gene promoter is activated by Brn-3b POU family transcription factor and not by Brn-3a or Brn-3c. J. Biol. Chem., 270(25), 15143 - 15147.

Milton, N.G.N. (1994) Effect of peripheral corticotrophin-releasing factors on febrile responses. In Temperature Regulation: Recent Physiological and Pharmacological Advances, Ed A.S. Milton, Birkhauser, Basel, pp 1 - 10.

Milton, N.G.N., Swanton, E. & Hillhouse, E.W. (1994) Pyrogenic immunomodulator stimulation of a novel thymic corticotrophin-releasing factor in vitro. In Temperature Regulation: Recent Physiological and Pharmacological Advances, Ed A.S. Milton, Birkhauser, Basel, pp 59 - 64.

Grammatopoulos, D., Milton, N.G.N. & Hillhouse, E.W. (1994) The human myometrial corticotropin-releasing hormone receptor: G proteins and second messengers. Mol. Cell. Endocrinol., 99(2), 245 - 250.

Milton, N.G.N., Hillhouse, E.W. & Milton, A.S. (1993) Does peripheral arginine vasopressin have a role in the febrile response of conscious rabbits? J. Physiol., 469, 525 - 534.

Hillhouse, E.W., Grammatopoulos, D., Milton, N.G.N. & Quartero, H.W.P. (1993) The identification of a human myometrial corticotropin-releasing hormone receptor which increases in affinity during pregnancy. J. Clin. Endocrinol. Metab., 76(3), 736 - 741.

Holland, A.J., Treasure, J., Coskeran, P., Dallow, J., Milton, N. & Hillhouse, E. (1993) Measurement of excessive appetite and metabolic changes in Prader-Willi syndrome. Int. J. Obes. Relat. Metab. Disord., 17(9), 527 - 532.

Milton, N.G.N., Hillhouse, E.W. & Milton, A.S. (1993) A possible role for peripheral corticotrophin-releasing factor-41 in the febrile response of conscious rabbits. J. Physiol., 465, 419 - 430.

Milton, N.G.N., Hillhouse, E.W. & Milton, A.S. (1993) Modulation of the prostaglandin responses of conscious rabbits to the pyrogen polyinosinic:polycytidylic acid by corticotrophin-releasing factor-41. J. Endocrinol., 138(1), 7 - 11.

Milton, N.G.N., Self, C.H. & Hillhouse, E.W. (1993) Effects of pyrogenic immunomodulators on the release of corticotrophin-releasing factor-41 and prostaglandin E2 from the intact rat hypothalamus in vitro. Br. J. Pharmacol., 109(1), 88 - 93.

Milton, N.G.N., Hillhouse, E.W. & Milton, A.S. (1992) Activation of the hypothalamo-pituitary-adrenocortical axis in the conscious rabbit by the pyrogen polyinosinic:polycytidylic acid is dependent on corticotrophin releasing factor-41. J. Endocrinol., 135(1), 69 - 75.

Milton, N.G.N., Nicholson, S.A., Self, C.H. & Hillhouse, E.W. (1990) The effects of rat corticotrophin releasing factor (CRF-41) peptide fragments on bioassay and immunoassay determination of CRF-41 levels. J. Neuroendocrinol., 2(6), 896 - 901.

Milton, N.G.N., Hillhouse, E.W., Fuller, J.Q. & Self, C.H. (1990) Corticotrophin releasing factor (CRF-41) in the human and rat - utility of a highly sensitive enzyme amplified immunometric assay. J. Neuroendocrinol., 2(6), 889 - 895.

Milton, N.G.N., Hillhouse, E.W., Nicholson, S.A., Self, C.H. & McGregor, A.M. (1990) Production and utilisation of monoclonal antibodies to human/rat corticotrophin releasing factor (CRF-41). J. Mol. Endocrinol., 5(2), 159 - 166.

Hillhouse, E.W. & Milton, N.G.N. (1989) The effect of acetylcholine and 5-hydroxytryptamine on the secretion of corticotrophin releasing factor-41 and arginine vasopressin from the rat hypothalamus in vitro. J. Endocrinol., 122(3), 713 - 718.

Hillhouse, E.W. & Milton, N.G.N. (1989) The effect of noradrenaline and gamma-aminobutyric acid on the secretion of corticotrophin releasing factor-41 and arginine vasopressin from the rat hypothalamus in vitro. J. Endocrinol., 122(3), 719 - 723.