Greenfield S.A., Garcia-Rates S.. When a trophic process turns toxic: Alzheimer’s disease as an aberrant recapitulation of a developmental mechanism, International Journal of Biochemistry and Cell Biology.2022. View PDF 

Greenfield S.A., Cole G.M., Coen C.W. , Frautschy S., Singh R.P., Mekkittikul M., Garcia-Rates S., Morrill P., Hollings O., Passmore M., Hasan S., Carty N., Bison S., Piccoli L., Carletti R., Tacconi S., Chalidou A., Pedercini M., Kroecher T., Astner H., Gerrard P.A.. A novel process driving Alzheimer’s disease validated in a mouse model: Therapeutic potential, Translational Research & Clinical Interventions. 2022.  View PDF

Ferrati G., Bion G., Harris A. J. and Greenfield S.A. Protective and reversal actions of a novel peptidomimetic against a pivotal toxin implicated in Alzheimer’s disease, Biomedicine & Pharmacotherapy, Volume 109, 2019, Pages 1052-1061. View PDF

Ferrati, G., Brai, E., Stuart, S., Marino, C. and Greenfield, S. (2018). A Multidisciplinary Approach Reveals an Age-Dependent Expression of a Novel Bioactive Peptide, Already Involved in Neurodegeneration, in the Postnatal Rat Forebrain. Brain Sciences, 8(7), p.132. View PDF

Brai, E., Simon, F., Cogoni, A. and Greenfield, S. (2018).”Modulatory Effects of a Novel Cyclized Peptide in Reducing the Expression of Markers Linked to Alzheimer’s Disease”. Frontiers in Neuroscience, [online] 12. View PDF

Pepper, C, Tu, H, Morrill, P, Garcia-Rates, S, Fegan, C and Greenfield, S. (2017)”Tumour cell migration is inhibited by a novel therapeutic strategy antagonising the alpha-7 receptor.” Oncotarget. 2017 Feb 14;8(7):11414-11424. doi: 10.18632/oncotarget.14545. View PDF

 Greenfield SA, Badin AS, Ferrati G, Devonshire IA. (2017) “Optical imaging of the rat brain suggests a previously missing link between top-down and bottom-up nervous system function.” Neurophoton. 4(3), 031213 (2017), doi: 10.1117/1.NPh.4.3.031213. View PDF

Garcia-Ratés, S and Greenfield SA (2017) “Cancer and neurodegeneration: two sides, same coin?” Oncotarget, 2017, Vol. 8, (No. 14), pp: 22307-22308 View PDF

Brai E, Stuart S, Badin AS & Greenfield SA. (2017) “A novel ex-vivo model to investigate the underlying mechanism in Alzheimer’s disease.” Front. Cell. Neurosci. Doi: 10.3389/fncel.2017.00291. View PDF

Badin, AS, Fermani, F and Greenfield, SA. (2017) “The features and functions of neuronal assemblies: possible dependency on mechanisms beyond synaptic transmission.” Front Neural Circuits. 2017 Jan 10;10:114. doi: 10.3389/fncir.2016.00114. eCollection 2016. View PDF

Garcia-Ratés, S, Morrill, P, Tu, H, Pottiez, G, Badin, A-S, Tormo-Garcia, C, Heffner, C, Coen, CW & Greenfield, SA. (2016) (I) “Pharmacological profiling of a novel modulator of the α7 nicotinic receptor: Blockade of a toxic acetylcholinesterase-derived peptide increased in Alzheimer brains.” Neuropharmacology, vol 105, pp. 487-499., 10.1016/j.neuropharm.2016.02.006. View PDF

Badin AS, Morrill P, Devonshire IM, Greenfield SA. (2016) (II) “Physiological profiling of an endogenous peptide in the basal forebrain: Age-related bioactivity and blockade with a novel modulator.” Neuropharmacology, 105:47-60. doi: 10.1016/j.neuropharm.2016.01.012. View PDF

Small GW, Greenfield S. (2015) “Current and Future Treatments for Alzheimer Disease.” Am J Geriatr Psychiatry. Nov; 23 (11):1101-5. doi: 10.1016/j.jagp.2015.08.006. View PDF

Greenfield SA (2013) “Discovering and targeting the basic mechanism of neurodegeneration: the role of peptides from the c-terminus of acetylcholinesterase Chemico-Biological Interactions”. 2013 May 25;203(3):543-6. doi: 10.1016/j.cbi.2013.03.015. Epub 2013 Apr 3. View PDF

Garcia-Ratés, S., Lewis, M., Worral R., & Greenfield S. A. (2013) “Additive Toxicity of β-Amyloid by aNovel Bioactive Peptide In Vitro: Possible Implications for Alzheimer’s Disease.” PLoS ONE 8(2):e54864. doi:10.1371/journal.pone.0054864 PLOS1. View PDF

Badin, S., Eraifej, J,. Greenfield, S. A. (2013) “High-resolution spatio-temporal bioactivity of a novel peptide revealed by optical imaging in rat orbitofrontal cortex in vitro: possible implications for neurodegenerative diseases”. Neuropharmacology. 2013 Oct;73:10-8. doi: 10.1016/j.neuropharm.2013.05.019. Epub 2013 May 24. View PDF

Halliday, A. C. & Greenfield, S. A. (2012) “From Protein to Peptides: a Spectrum of Non-Hydrolytic Functions of Acetylcholinesterase”. Protein & Peptide Letters 19, 165-172, doi:10.2174/092986612799080149. View PDF

Halliday, A. C., Kim, O., Bond, C. E. & Greenfield, S. A. (2010) “Evaluation of a technique to identify acetylcholinesterase C-terminal peptides in human serum samples”. Chem-Biol Interact 187, 110-114, doi:10.1016/j.cbi.2010.02.010. View PDF

Bond, C. E., Zimmermann, M. & Greenfield, S. A. (2009) “Upregulation of alpha 7 Nicotinic Receptors by Acetylcholinesterase C-Terminal Peptides.” Plos One 4, -, doi:Artn E4846 Doi 0.1371/Journal.Pone.0004846. View PDF

Zimmerman, M., Grosgen, S., Westwell, M. S. & Greenfield, S. A. (2008) “Selective enhancement of the activity of C-terminally truncated, but not intact, acetylcholinesterase.” J Neurochem 104, 221-232, doi:DOI 10.1111/j.1471-4159.2007.05045.x. View PDF

Greenfield, S. A., Zimmermann, M. & Bond, C. E. (2008) “Non-hydrolytic functions of acetylcholinesterase – The significance of C-terminal peptides.” Febs J 275, 604-611, doi:DOI 10.1111/j.1742-4658.2007.06235.x. View PDF

Greenfield SA, Zimmermann M. and Bond CE. (2008) “Non-hydrolytic functions of ACHE: The significance of C-terminal peptides”. Federation of European Biochemical Societies. FEBS Journal 275, pp 604-611. View PDF

Bond, C. E. & Greenfield, S. A. (2007) “Multiple cascade effects of oxidative stress on astroglia” Glia 55, 1348-1361, doi:Doi 10.1002/Glia.20547. View PDF

Onganer, P. U., Djamgoz, M. B. A., Whyte, K. & Greenfield, S. A. (2006) “An acetylcholinesterasederived peptide inhibits endocytic membrane activity in a human metastatic breast cancer cell line.” Bba-Gen Subjects 1760, 415-420, doi:DOI 10.1016/j.bbagen.2005.12.016. View PDF

Mann, E. O., Tominaga, T., Ichikawa, M. & Greenfield, S. A. (2005) “Cholinergic modulation of the spatiotemporal pattern of hippocampal activity in vitro.” Neuropharmacology 48, 118-133, doi:DOI 10.1016/j.neuropharm.2004.08.022. View PDF

Greenfield SA (2005) “A peptide derived from acetylcholinesterase is a pivotal signaling molecule in neurodegeneration.” Chemico-Biological Interactions Vol 157-158, pp 122-218. View PDF

Zabarsky, V., Thomas, J. & Greenfield, S. (2004) “Bioactivity of a peptide derived from acetylcholinesterase: involvement of an ivermectin-sensitive site on the alpha 7 nicotinic receptor.” Neurobiology of Disease 16, 283-289, doi:10.1016/j.nbd.2004.02.009. View PDF

Greenfield, S. A., Day, T., Mann, E. O. & Bermudez, I. (2004) “A novel peptide modulates alpha 7 nicotinic receptor responses: implications for a possible trophic-toxic mechanism within the brain”. J Neurochem 90, 325-331, doi:DOI 10.1111/j.1471-4159.2004.02494.x. View PDF

Emmett, S. R. & Greenfield, S. A. (2004) “A peptide derived from the C-terminal region of acetylcholinesterase modulates extracellular concentrations of acetylcholinesterase in the rat substantia nigra.” Neurosci Lett 358, 210-214, doi:DOI 10.1016/j.neulet.2003.12.078. View PDF

Day, T. & Greenfield, S. A. (2004) “Bioactivity of a peptide derived from acetylcholinesterase in hippocampal organotypic cultures”. Exp Brain Res 155, 500-508, doi:DOI 10.1007/s00221-003-1757-1. View PDF

Whyte, K. A. & Greenfield, S. A. (2003) “Effects of acetylcholinesterase and butyrylcholinesterase on cell survival, neurite outgrowth, and voltage-dependent calcium currents of embryonic ventral mesencephalic neurons.” Exp Neurol 184, 496-509, doi:Doi 10.1016/S0014-4886(03)00386-8. View PDF

Day, T. & Greenfield, S. A. (2003) “A peptide derived from acetylcholinesterase induces neuronal cell death: characterisation of possible mechanisms.” Exp Brain Res 153, 334-342, doi:DOI 10.1007/s00221-003-1567-5. View PDF

Bon, C. L. M. & Greenfield, S. A. (2003) “Bioactivity of a peptide derived from acetylcholinesterase: electrophysiological characterization in guinea-pig hippocampus.” Eur J Neurosci 17, 1991-1995, doi:DOI 10.1046/j.1460-9568.2003.02648.x. View PDF

Greenfield, S. & Vaux, D. J. (2002) “Parkinson’s disease, Alzheimer’s disease and motor neurone disease: Identifying a common mechanism.” Neuroscience 113, 485-492. View PDF

Day, T. & Greenfield, S. A. (2002) “A non-cholinergic, trophic action of acetylcholinesterase on hippocampal neurones in vitro: Molecular mechanisms.” Neuroscience 111, 649-656, doi:Pii S0306-4522(02)00031-3. View PDF

Background Reviews of Research Leading to the Discovery of T14

Greenfield, SA (1998) A non-cholinergic function for AChE in the substantia nigra. In Structure and function of cholinesterases and related proteins. Eds Doctor, BP, et el. Plenum Press, New York, pp 557-562. View PDF

Greenfield, SA (1996) Non-classical actions of cholinesterases: role in cellular differentiation, tumorigenesis and Alzheimer’s disease: A Critique. Neurochem. Int. Vol. 28, pp 485-490. View PDF

Greenfield, SA (1991) A non-cholinergic action of AChE in the brain: from neuronal secretion to the generation of movement. Cell. and Mol. Neurobiol. 11, pp 55-57. PDF

Greenfield, SA (1985) The significance of dendritic release of transmitter and protein in the substantia nigra. Neurochem. Int. 7, pp 887-901. View PDF

Greenfield, SA (1984) Acetylcholinesterase may have novel functions in the brain. Trends in Neuroscience 7, No 10, pp 364-368. View PDF

Supporting Publications from Other Labs

Mohs R. and Greig N. (2017) “Drug discovery and development: Role of basic biological research”Alzheimer’s & Dementia: Tranlational Research & Clinical Interventions, 3 (4) 651-657

Horvath et al. (2014) “Neuropathology of Parkinsonism in patients with pure Alzheimer’s disease.” J Alzheimers Dis. 39 (1): 115-20.

Garcia-Ayllón, M.-S., E. Llorens, J. Avila, J. Alom and J. Saez-Valero (2014) “Elevated Acetylcholinesterase Levels by Hyperphosphorylated Tau Overexpression.” Alzheimer’s & Dementia 10(4): P651.

Trillo et al. (2013) “Ascending monoaminergic systems alterations in Alzheimer’s disease, translantic basic science into clinical care.” Neurosci Biobehav Rev. 37 (8): 1363-79.

Irwin, D. J., Lee, V. M. & Trojanowski, J. Q.” Parkinson’s disease dementia: convergence of alpha synuclein, tau and amyloid-beta pathologies” (2013) Nature reviews. Neuroscience 14, 626-636,

Szot (2012) “Common factors among Alzheimer’s disease, Parkinson disease, and epilepsy: possible role of the noradrenergic nervous system.” Epilepsi 53 (1): 61-6.

Morgan et al. (2012) “Can the flow of medicines be improved? Fundametnal pharmacokinetic and pharmacological principles towards improving Phase II survival” Drug Discovery Today. 17(9-10) 419-424

Braak & Del Tredici. (2012) “Where, when, and in what form does sporadic Alzheimer’s disease begin?” Curr opin Neurol. 25 (6): 708-14.

Attems et al. (2012) “The relationship between subcortical tau pathology and Alzheimer’s disease”. Biochem Soc Trans. 40 (4): 711-5.

Lea Tenenholz Grinberg, Udo Rueb and Helmut Heinsen. (2011) “Brainstem: Neglected Locus in Neurodegenerative Diseases.” Front Neuro); 2: 42.

Garcia-Ayllon, M. S., D. H. Small, J. Avila and J. Saez-Valero (2011) “Revisiting the Role of Acetylcholinesterase in Alzheimer’s Disease: Cross-Talk with P-tau and beta-Amyloid.” Front Mol Neurosci 4: 22.

Braak et al. (2011) “Stages of the Pathologic Process in Alzheimer Disease: Age Categories From 1 to 100 Years.” Journal of Neuropathology & Experimental Neurology. 70(11):960-969.

Braak & Del Tredici (2011) “Alzheimer’s pathogenesis: is there neuron-to-neuron propagation? Acta neuropathol.” 121 (5): 589-95.

Garcia-Ayllon, M. S., I. Riba-Llena, C. Serra-Basante, J. Alom, R. Boopathy and J. Saez-Valero (2010) “Altered levels of acetylcholinesterase in Alzheimer plasma.” PLoS One 5(1): e8701.

Simic et al. (2009) “Does Alzheimer’s disease begin in the brainstem?” Neuropathol Appl Neuobiol. 35 (6): 532-54.

Weinshenker (2008) “Functional consequences of locus coeruleus degeneration in Alzheimer’s disease.” Curr Alzheimer Res 5 (3): 342-5.

Haglund et al. (2006) “Locus coeruleus degeneration is ubiquitous in Alzheimer’s disease: possible implications for diagnosis and treatment.Neurophatology” 26 (6): 528-32.

Bond, C. E. et al. (2006) “Astroglia up-regulate transcription and secretion of ‘readthrough’ acetylcholinesterase following oxidative stress.” Eur J Neurosci 24, 381-386, doi:DOI 10.1111/j.1460-9568.2006.04989.x.

Zarow et al. (2003) “Neuronal loss is greater in the locus coeruleus than nucleus basalis and substantia nigra in Alzheimers and Parkinson diseases.” Arch Neurol 60 (30): 337-41.

Woolf, N. J. (1996) “Global and serial neurons form A hierarchically arranged interface proposed to underlie memory and cognition.” Neuroscience 74(3): 625-651.

Arendt, T., M. K. Bruckner, M. Lange and V. Bigl (1992) “Changes in acetylcholinesterase and butyrylcholinesterase in Alzheimer’s disease resemble embryonic development–a study of molecular forms.” Neurochem Int 21(3): 381-396.

Card, J. P., R. P. Meade and L. G. Davis (1988) “Immunocytochemical localization of the precursor protein for beta-amyloid in the rat central nervous system.” Neuron 1(9): 835-846.

Bondareff et al. (1987) “Neuronal degeneration in locus coreuleus and cortical correlates of Alzheimers disease.” Arch Neurol 60 (3): 337-41.

Rossor MN. (1981) “Parkinson’s disease and Alzheimer’s disease as disorders of the isodendritic core.” Br Med J (Clin Res Ed). 19 Dec 12;283(6306):1588-90.

Liu, C. C., Liu, C. C., Kanekiyo, T., Xu, H., & Bu, G. (2013). Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nature reviews. Neurology, 9:106–118.

Makin S. (2018). The amyloid hypothesis on trial. Nature, 559:S4–S7.

Iqbal, K., Liu, F., Gong, C. X., & Grundke-Iqbal, I. (2010). Tau in Alzheimer disease and related tauopathies. Current Alzheimer research, 7:656–664.

Wyss-Coray, T., & Rogers, J. (2012). Inflammation in Alzheimer disease-a brief review of the basic science and clinical literature. Cold Spring Harbor perspectives in medicine, 2:a006346.

Seguela, P., J. Wadiche, K. Dineley-Miller, J. A. Dani and J. W. Patrick (1993). Molecular cloning, functional properties, and distribution of rat brain alpha 7: a nicotinic cation channel highly permeable to calcium. J Neurosci 13:596-604.

Svedberg, M. M., A. L. Svensson, M. Johnson, M. Lee, O. Cohen, J. Court, H. Soreq, E. Perry and A. Nordberg (2002). Upregulation of neuronal nicotinic receptor subunits alpha4, beta2, and alpha7 in transgenic mice overexpressing human acetylcholinesterase. J Mol Neurosci 18:211-222.

Dineley, K. T., Westerman, M., Bui, D., Bell, K., Ashe, K. H., & Sweatt, J. D. (2001). Beta-amyloid activates the mitogen-activated protein kinase cascade via hippocampal alpha7 nicotinic acetylcholine receptors: In vitro and in vivo mechanisms related to Alzheimer’s disease. The Journal of neuroscience: the official journal of the Society for Neuroscience, 21:4125–4133.

Akerman, C., Hossain, S., Shobo, A.O., and Zhong, Y. (2019) Neurodegenerative Disease-Related Proteins within the Epidermal Layer of the Human Skin. Journal of Alzheimer’s disease: JAD 69:1-16

Broide, R. S., R. T. Robertson and F. M. Leslie (1996). Regulation of alpha7 nicotinic acetylcholine receptors in the developing rat somatosensory cortex by thalamocortical afferents. J Neurosci 16:2956-2971.

Dickinson, J. A., K. E. Hanrott, M. H. Mok, J. N. Kew and S. Wonnacott (2007). Differential coupling of alpha7 and non-alpha7 nicotinic acetylcholine receptors to calcium-induced calcium release and voltage-operated calcium channels in PC12 cells. J Neurochem 100: 1089-1096.

Morris, G. P., Clark, I. A., & Vissel, B. (2014). Inconsistencies and controversies surrounding the amyloid hypothesis of Alzheimer’s disease. Acta neuropathologica communications, 2:135

Butcher, L. L., & Woolf, N. J. (1989). Neurotrophic agents may exacerbate the pathologic cascade of Alzheimer’s disease. Neurobiology of aging, 10: 557–570.


T: +44 (0)1235 420 085

NBO logo

© All Rights Reserved NeuroBio

ArabicChinese (Simplified)EnglishRussian
NeuroBio logo

Subscribe To Our Newsletter

Join our mailing list to receive the latest news and updates from Neuro-Bio

You have Successfully Subscribed!