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Scientific reports2021; 11(1); 16036; doi: 10.1038/s41598-021-95396-7

Equine pituitary pars intermedia dysfunction: a spontaneous model of synucleinopathy.

Abstract: Equine pituitary pars intermedia dysfunction (PPID) is a common endocrine disease of aged horses that shows a similar pathophysiology as Parkinson's Disease (PD) with increased levels of α-synuclein (α-syn). While α-syn is thought to play a pathogenic role in horses with PPID, it is unclear if α-syn is also misfolded in the pars intermedia and could similarly promote self-aggregation and propagation. Consequently, α-syn was isolated from the pars intermedia from groups of healthy young and aged horses, and aged PPID-afflicted horses. Seeding experiments confirmed the prion-like properties of α-syn isolated from PPID-afflicted horses. Next, detection of α-syn fibrils in pars intermedia via transmission electron microscopy (TEM) was exclusive to PPID-afflicted horses. A bank of fragment peptides was designed to further characterize equine α-syn misfolding. Region 62-87 of equine and human α-syn peptides was found to be most prone to aggregation according to Tango bioinformatic program and kinetics of aggregation via a thioflavin T fluorescence assay. In both species, fragment peptide 62-87 is capable of generating mature fibrils as demonstrated by TEM. The combined animal, bioinformatic, and biophysical studies provide evidence that equine α-syn is misfolded in PPID horses.
© 2021. The Author(s).
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Publication Date: 2021-08-06 PubMed ID: 34362943PubMed Central: PMC8346493DOI: 10.1038/s41598-021-95396-7Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research explores the connection between a common endocrine disorder in horses called Equine pituitary pars intermedia dysfunction (PPID) and Parkinson’s Disease. The study found evidence suggesting misfolded α-synuclein proteins involved in PPID horses could reflect characteristics observed in Parkinson’s Disease, hinting at potential similarities in pathophysiology.

Introduction and Experiment Overview

  • The study aims to understand the role of a protein known as α-synuclein (α-syn) in Equine pituitary pars intermedia dysfunction (PPID), a disease common in aging horses.
  • Earlier research has highlighted an overproduction of α-syn in PPID much in the same way it is overproduced in Parkinson’s Disease (PD), a neurological disorder in humans. However, questions remained about whether the overproduction of α-syn in PPID horses led to its misfolding, as is known to occur in PD.
  • The researchers isolated α-syn from the pars intermedia (a part of the pituitary gland) in healthy young horses, aged horses, and aged PPID-afflicted horses to investigate this.

Findings: Prion-Like Properties and Detection of α-syn fibrils

  • A series of seeding experiments revealed that the α-syn protein isolated from the PPID-afflicted horses demonstrated prion-like properties, potentially indicating that the protein was indeed misfolded.
  • Further confirmation was found through the use of transmission electron microscopy (TEM), where the detection of misfolded α-syn fibrils was exclusive to PPID-afflicted horses.

Fragment Peptide Study and Bioinformatic Analysis

  • Researchers created a collection of fragment peptides to better understand the process and characteristics of α-syn protein misfolding in the horses.
  • Using a Tango bioinformatic program, they found a specific region (62-87) of the equine and human α-syn peptides that was particularly prone to aggregation, indicative of misfolding.
  • This result was further supported by a fluorescence assay using thioflavin T, demonstrating the kinetics of aggregation.
  • In both equine and human α-syn peptides, fragment peptide 62-87 was noted to be capable of producing mature fibrils, a significant marker for misfolded proteins, further characterized by the TEM.

Conclusion

  • The combined findings from the animal studies, bioinformatics evaluation, and biophysical evidence led researchers to conclude that α-syn misfolding occurs in PPID-afflicted horses, replicating a significant characteristic of Parkinson’s Disease.
  • This research points to a spontaneous model of synucleinopathy in horses mirroring human diseases like PD, offering potential avenues for future therapeutic research and development in human and veterinary medicine.

Cite This Article

APA
Fortin JS, Hetak AA, Duggan KE, Burglass CM, Penticoff HB, Schott HC. (2021). Equine pituitary pars intermedia dysfunction: a spontaneous model of synucleinopathy. Sci Rep, 11(1), 16036. https://doi.org/10.1038/s41598-021-95396-7

Publication

Scientific reports
ISSN: 2045-2322
NlmUniqueID: 101563288
Country: England
Language: English
Volume: 11
Issue: 1
Pages: 16036
PII: 16036

Researcher Affiliations

Fortin, Jessica S
  • Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI, 48824, USA. fortinj1@msu.edu.
Hetak, Ashley A
  • Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI, 48824, USA.
Duggan, Kelsey E
  • Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI, 48824, USA.
Burglass, Caroline M
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI, 48824, USA.
Penticoff, Hailey B
  • Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI, 48824, USA.
Schott, Harold C
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI, 48824, USA. schott@msu.edu.

MeSH Terms

  • Aging
  • Animals
  • Disease Models, Animal
  • Horse Diseases / metabolism
  • Horse Diseases / pathology
  • Horses
  • Pituitary Diseases / pathology
  • Pituitary Diseases / veterinary
  • Pituitary Gland, Intermediate / pathology
  • Synucleinopathies / physiopathology
  • alpha-Synuclein / metabolism

Conflict of Interest Statement

The authors declare no competing interests.

References

This article includes 56 references
  1. Marras C, Beck JC, Bower JH, Roberts E, Ritz B, Ross GW, Abbott RD, Savica R, Van Den Eeden SK, Willis AW, Tanner CM. Prevalence of Parkinson's disease across North America.. NPJ Parkinsons Dis 2018;4:21.
    doi: 10.1038/s41531-018-0058-0pmc: PMC6039505pubmed: 30003140google scholar: lookup
  2. Casajus Pelegay E, Puzzo F, Yilmazer A, Cagin U. Targeting Mitochondrial Defects to Increase Longevity in Animal Models of Neurodegenerative Diseases.. Adv Exp Med Biol 2019;1134:89-110.
    doi: 10.1007/978-3-030-12668-1_5pubmed: 30919333google scholar: lookup
  3. Dawson TM, Golde TE, Lagier-Tourenne C. Animal models of neurodegenerative diseases.. Nat Neurosci 2018 Oct;21(10):1370-1379.
    doi: 10.1038/s41593-018-0236-8pmc: PMC6615039pubmed: 30250265google scholar: lookup
  4. Fernandez CI, López J, Martinez L. Non-Clinical Models for Neurodegenerative Diseases: Therapeutic Approach and Drug Validation in Animal Models.. Behav Sci (Basel) 2017 Dec;7(4):82.
    doi: 10.3390/bs7040082pmc: PMC5746691pubmed: 29299350google scholar: lookup
  5. Guyer C. Recent developments in animal models of human neurodegenerative diseases.. Toxicol Pathol 2000 Mar-Apr;28(2):363-6.
    doi: 10.1177/019262330002800218pubmed: 10805156google scholar: lookup
  6. Jucker M. The benefits and limitations of animal models for translational research in neurodegenerative diseases.. Nat Med 2010 Nov;16(11):1210-4.
    doi: 10.1038/nm.2224pubmed: 21052075google scholar: lookup
  7. Kahle PJ, Haass C. The emerging utility of animal models of chronic neurodegenerative diseases.. Expert Opin Ther Targets 2001 Feb;5(1):125-32.
    pubmed: 15992171doi: 10.1517/14728222.5.1.125google scholar: lookup
  8. Kasparová S, Sumbalová Z, Horecký J, Bystrický P, Mlynárik V, Gvozdjáková A, Liptaj T. New magnetic resonance spectroscopy biomarker for monitoring neurodegenerative diseases: animal models.. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2005 Dec;149(2):373-6.
    doi: 10.5507/bp.2005.061pubmed: 16601791google scholar: lookup
  9. Kurniawan ND. MRI in the Study of Animal Models of Neurodegenerative Diseases.. Methods Mol Biol 2018;1718:347-375.
    doi: 10.1007/978-1-4939-7531-0_21pubmed: 29341019google scholar: lookup
  10. Moreno-Gonzalez I, Soto C. Natural animal models of neurodegenerative protein misfolding diseases.. Curr Pharm Des 2012;18(8):1148-58.
    doi: 10.2174/138161212799315768pubmed: 22288404google scholar: lookup
  11. Nithianantharajah J, Hannan AJ. Mechanisms mediating brain and cognitive reserve: experience-dependent neuroprotection and functional compensation in animal models of neurodegenerative diseases.. Prog Neuropsychopharmacol Biol Psychiatry 2011 Mar 30;35(2):331-9.
    doi: 10.1016/j.pnpbp.2010.10.026pubmed: 21112312google scholar: lookup
  12. Ribeiro FM, Camargos ER, de Souza LC, Teixeira AL. Animal models of neurodegenerative diseases.. Braz J Psychiatry 2013;35 Suppl 2:S82-91.
    doi: 10.1590/1516-4446-2013-1157pubmed: 24271230google scholar: lookup
  13. Soto C. Animal models for neurodegenerative diseases associated to accumulation of misfolded protein aggregates.. Curr Pharm Des 2012;18(8):1107.
    doi: 10.2174/138161212799315803pubmed: 22288399google scholar: lookup
  14. Ugarte A, Corbacho D, Aymerich MS, García-Osta A, Cuadrado-Tejedor M, Oyarzabal J. Impact of Neurodegenerative Diseases on Drug Binding to Brain Tissues: From Animal Models to Human Samples.. Neurotherapeutics 2018 Jul;15(3):742-750.
    doi: 10.1007/s13311-018-0624-5pmc: PMC6095788pubmed: 29675823google scholar: lookup
  15. Youssef SA, Capucchio MT, Rofina JE, Chambers JK, Uchida K, Nakayama H, Head E. Pathology of the Aging Brain in Domestic and Laboratory Animals, and Animal Models of Human Neurodegenerative Diseases.. Vet Pathol 2016 Mar;53(2):327-48.
    doi: 10.1177/0300985815623997pubmed: 26869150google scholar: lookup
  16. Schott HC 2nd. Pituitary pars intermedia dysfunction: equine Cushing's disease.. Vet Clin North Am Equine Pract 2002 Aug;18(2):237-70.
    doi: 10.1016/S0749-0739(02)00018-4pubmed: 15635907google scholar: lookup
  17. McFarlane D, Dybdal N, Donaldson MT, Miller L, Cribb AE. Nitration and increased alpha-synuclein expression associated with dopaminergic neurodegeneration in equine pituitary pars intermedia dysfunction.. J Neuroendocrinol 2005 Feb;17(2):73-80.
    doi: 10.1111/j.1365-2826.2005.01277.xpubmed: 15796757google scholar: lookup
  18. Love S. Equine Cushing's disease.. Br Vet J 1993 Mar-Apr;149(2):139-53.
    doi: 10.1016/S0007-1935(05)80084-3pubmed: 8485640google scholar: lookup
  19. Kirik D, Rosenblad C, Burger C, Lundberg C, Johansen TE, Muzyczka N, Mandel RJ, Björklund A. Parkinson-like neurodegeneration induced by targeted overexpression of alpha-synuclein in the nigrostriatal system.. J Neurosci 2002 Apr 1;22(7):2780-91.
    doi: 10.1523/JNEUROSCI.22-07-02780.2002pmc: PMC6758323pubmed: 11923443google scholar: lookup
  20. Bendor JT, Logan TP, Edwards RH. The function of α-synuclein.. Neuron 2013 Sep 18;79(6):1044-66.
    doi: 10.1016/j.neuron.2013.09.004pmc: PMC3866954pubmed: 24050397google scholar: lookup
  21. Somayaji M, Cataldi S, Choi SJ, Edwards RH, Mosharov EV, Sulzer D. A dual role for α-synuclein in facilitation and depression of dopamine release from substantia nigra neurons in vivo.. Proc Natl Acad Sci U S A 2020 Dec 22;117(51):32701-32710.
    doi: 10.1073/pnas.2013652117pmc: PMC7768743pubmed: 33273122google scholar: lookup
  22. Conway KA, Lee SJ, Rochet JC, Ding TT, Williamson RE, Lansbury PT Jr. Acceleration of oligomerization, not fibrillization, is a shared property of both alpha-synuclein mutations linked to early-onset Parkinson's disease: implications for pathogenesis and therapy.. Proc Natl Acad Sci U S A 2000 Jan 18;97(2):571-6.
    doi: 10.1073/pnas.97.2.571pmc: PMC15371pubmed: 10639120google scholar: lookup
  23. Gilgun-Sherki Y, Melamed E, Offen D. Oxidative stress induced-neurodegenerative diseases: the need for antioxidants that penetrate the blood brain barrier.. Neuropharmacology 2001 Jun;40(8):959-75.
    doi: 10.1016/S0028-3908(01)00019-3pubmed: 11406187google scholar: lookup
  24. HORNYKIEWICZ O. [The tropical localization and content of noradrenalin and dopamine (3-hydroxytyramine) in the substantia nigra of normal persons and patients with Parkinson's disease].. Wien Klin Wochenschr 1963 May 3;75:309-12.
    pubmed: 13954967
  25. Spelta CW. Equine pituitary pars intermedia dysfunction: current perspectives on diagnosis and management.. Vet Med (Auckl) 2015;6:293-300.
    pmc: PMC6067528pubmed: 30101114doi: 10.2147/VMRR.S74191google scholar: lookup
  26. Couëtil L, Paradis MR, Knoll J. Plasma adrenocorticotropin concentration in healthy horses and in horses with clinical signs of hyperadrenocorticism.. J Vet Intern Med 1996 Jan-Feb;10(1):1-6.
    doi: 10.1111/j.1939-1676.1996.tb02016.xpubmed: 8965262google scholar: lookup
  27. Heinrichs M, Baumgärtner W, Capen CC. Immunocytochemical demonstration of proopiomelanocortin-derived peptides in pituitary adenomas of the pars intermedia in horses.. Vet Pathol 1990 Nov;27(6):419-25.
    doi: 10.1177/030098589902700606pubmed: 2177580google scholar: lookup
  28. Millington WR, Dybdal NO, Dawson R Jr, Manzini C, Mueller GP. Equine Cushing's disease: differential regulation of beta-endorphin processing in tumors of the intermediate pituitary.. Endocrinology 1988 Sep;123(3):1598-604.
    doi: 10.1210/endo-123-3-1598pubmed: 2456916google scholar: lookup
  29. Brosnahan MM, Paradis MR. Demographic and clinical characteristics of geriatric horses: 467 cases (1989-1999).. J Am Vet Med Assoc 2003 Jul 1;223(1):93-8.
    doi: 10.2460/javma.2003.223.93pubmed: 12839071google scholar: lookup
  30. Innerå M, Petersen AD, Desjardins DR, Steficek BA, Rosser EJ Jr, Schott HC 2nd. Comparison of hair follicle histology between horses with pituitary pars intermedia dysfunction and excessive hair growth and normal aged horses.. Vet Dermatol 2013 Feb;24(1):212-7.e46-7.
    doi: 10.1111/j.1365-3164.2012.01080.xpubmed: 23331700google scholar: lookup
  31. van der Kolk JH, Kalsbeek HC, van Garderen E, Wensing T, Breukink HJ. Equine pituitary neoplasia: a clinical report of 21 cases (1990-1992).. Vet Rec 1993 Dec 11;133(24):594-7.
    pubmed: 8116170
  32. Miller MA, Pardo ID, Jackson LP, Moore GE, Sojka JE. Correlation of pituitary histomorphometry with adrenocorticotrophic hormone response to domperidone administration in the diagnosis of equine pituitary pars intermedia dysfunction.. Vet Pathol 2008 Jan;45(1):26-38.
    doi: 10.1354/vp.45-1-26pubmed: 18192571google scholar: lookup
  33. McFarlane D. Advantages and limitations of the equine disease, pituitary pars intermedia dysfunction as a model of spontaneous dopaminergic neurodegenerative disease.. Ageing Res Rev 2007 May;6(1):54-63.
    doi: 10.1016/j.arr.2007.02.001pubmed: 17374512google scholar: lookup
  34. Gade Malmos K, Blancas-Mejia LM, Weber B, Buchner J, Ramirez-Alvarado M, Naiki H, Otzen D. ThT 101: a primer on the use of thioflavin T to investigate amyloid formation.. Amyloid 2017 Mar;24(1):1-16.
    doi: 10.1080/13506129.2017.1304905pubmed: 28393556google scholar: lookup
  35. Rousseau F, Schymkowitz J, Serrano L. Protein aggregation and amyloidosis: confusion of the kinds?. Curr Opin Struct Biol 2006 Feb;16(1):118-26.
    doi: 10.1016/j.sbi.2006.01.011pubmed: 16434184google scholar: lookup
  36. Fernandez-Escamilla AM, Rousseau F, Schymkowitz J, Serrano L. Prediction of sequence-dependent and mutational effects on the aggregation of peptides and proteins.. Nat Biotechnol 2004 Oct;22(10):1302-6.
    doi: 10.1038/nbt1012pubmed: 15361882google scholar: lookup
  37. Linding R, Schymkowitz J, Rousseau F, Diella F, Serrano L. A comparative study of the relationship between protein structure and beta-aggregation in globular and intrinsically disordered proteins.. J Mol Biol 2004 Sep 3;342(1):345-53.
    doi: 10.1016/j.jmb.2004.06.088pubmed: 15313629google scholar: lookup
  38. McFarlane D, Cribb AE. Systemic and pituitary pars intermedia antioxidant capacity associated with pars intermedia oxidative stress and dysfunction in horses.. Am J Vet Res 2005 Dec;66(12):2065-72.
    doi: 10.2460/ajvr.2005.66.2065pubmed: 16379648google scholar: lookup
  39. Fortin JS, Benskey MJ, Lookingland KJ, Patterson JS, Howey EB, Goudreau JL, Schott HC 2nd. Restoring pars intermedia dopamine concentrations and tyrosine hydroxylase expression levels with pergolide: evidence from horses with pituitary pars intermedia dysfunction.. BMC Vet Res 2020 Sep 25;16(1):356.
    doi: 10.1186/s12917-020-02565-3pmc: PMC7517620pubmed: 32977825google scholar: lookup
  40. Goudreau JL, Falls WM, Lookingland KJ, Moore KE. Periventricular-hypophysial dopaminergic neurons innervate the intermediate but not the neural lobe of the rat pituitary gland.. Neuroendocrinology 1995 Aug;62(2):147-54.
    doi: 10.1159/000126999pubmed: 8584114google scholar: lookup
  41. Saiardi A, Borrelli E. Absence of dopaminergic control on melanotrophs leads to Cushing's-like syndrome in mice.. Mol Endocrinol 1998 Aug;12(8):1133-9.
    pubmed: 9717839doi: 10.1210/mend.12.8.0144google scholar: lookup
  42. Kalia LV, Lang AE. Parkinson's disease.. Lancet 2015 Aug 29;386(9996):896-912.
    doi: 10.1016/S0140-6736(14)61393-3pubmed: 25904081google scholar: lookup
  43. Wong YC, Krainc D. α-synuclein toxicity in neurodegeneration: mechanism and therapeutic strategies.. Nat Med 2017 Feb 7;23(2):1-13.
    doi: 10.1038/nm.4269pubmed: 28170377google scholar: lookup
  44. Pieri L, Madiona K, Bousset L, Melki R. Fibrillar α-synuclein and huntingtin exon 1 assemblies are toxic to the cells.. Biophys J 2012 Jun 20;102(12):2894-905.
    doi: 10.1016/j.bpj.2012.04.050pmc: PMC3379023pubmed: 22735540google scholar: lookup
  45. Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, Pike B, Root H, Rubenstein J, Boyer R, Stenroos ES, Chandrasekharappa S, Athanassiadou A, Papapetropoulos T, Johnson WG, Lazzarini AM, Duvoisin RC, Di Iorio G, Golbe LI, Nussbaum RL. Mutation in the alpha-synuclein gene identified in families with Parkinson's disease.. Science 1997 Jun 27;276(5321):2045-7.
    doi: 10.1126/science.276.5321.2045pubmed: 9197268google scholar: lookup
  46. Krüger R, Kuhn W, Müller T, Woitalla D, Graeber M, Kösel S, Przuntek H, Epplen JT, Schöls L, Riess O. Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease.. Nat Genet 1998 Feb;18(2):106-8.
    doi: 10.1038/ng0298-106pubmed: 9462735google scholar: lookup
  47. Zarranz JJ, Alegre J, Gómez-Esteban JC, Lezcano E, Ros R, Ampuero I, Vidal L, Hoenicka J, Rodriguez O, Atarés B, Llorens V, Gomez Tortosa E, del Ser T, Muñoz DG, de Yebenes JG. The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia.. Ann Neurol 2004 Feb;55(2):164-73.
    doi: 10.1002/ana.10795pubmed: 14755719google scholar: lookup
  48. Appel-Cresswell S, Vilarino-Guell C, Encarnacion M, Sherman H, Yu I, Shah B, Weir D, Thompson C, Szu-Tu C, Trinh J, Aasly JO, Rajput A, Rajput AH, Jon Stoessl A, Farrer MJ. Alpha-synuclein p.H50Q, a novel pathogenic mutation for Parkinson's disease.. Mov Disord 2013 Jun;28(6):811-3.
    doi: 10.1002/mds.25421pubmed: 23457019google scholar: lookup
  49. Proukakis C, Dudzik CG, Brier T, MacKay DS, Cooper JM, Millhauser GL, Houlden H, Schapira AH. A novel α-synuclein missense mutation in Parkinson disease.. Neurology 2013 Mar 12;80(11):1062-4.
    doi: 10.1212/WNL.0b013e31828727bapmc: PMC3653201pubmed: 23427326google scholar: lookup
  50. Lesage S, Anheim M, Letournel F, Bousset L, Honoré A, Rozas N, Pieri L, Madiona K, Dürr A, Melki R, Verny C, Brice A. G51D α-synuclein mutation causes a novel parkinsonian-pyramidal syndrome.. Ann Neurol 2013 Apr;73(4):459-71.
    doi: 10.1002/ana.23894pubmed: 23526723google scholar: lookup
  51. Pasanen P, Myllykangas L, Siitonen M, Raunio A, Kaakkola S, Lyytinen J, Tienari PJ, Pöyhönen M, Paetau A. Novel α-synuclein mutation A53E associated with atypical multiple system atrophy and Parkinson's disease-type pathology.. Neurobiol Aging 2014 Sep;35(9):2180.e1-5.
    doi: 10.1016/j.neurobiolaging.2014.03.024pubmed: 24746362google scholar: lookup
  52. Dettmer U, Newman AJ, Soldner F, Luth ES, Kim NC, von Saucken VE, Sanderson JB, Jaenisch R, Bartels T, Selkoe D. Parkinson-causing α-synuclein missense mutations shift native tetramers to monomers as a mechanism for disease initiation.. Nat Commun 2015 Jun 16;6:7314.
    doi: 10.1038/ncomms8314pmc: PMC4490410pubmed: 26076669google scholar: lookup
  53. Sahin C, Kjær L, Christensen MS, N Pedersen J, Christiansen G, Pérez AW, Møller IM, Enghild JJ, Pedersen JS, Larsen K, Otzen DE. α-Synucleins from Animal Species Show Low Fibrillation Propensities and Weak Oligomer Membrane Disruption.. Biochemistry 2018 Aug 28;57(34):5145-5158.
    doi: 10.1021/acs.biochem.8b00627pubmed: 30067901google scholar: lookup
  54. Fortin JS, Benoit-Biancamano MO. Wildlife sequences of islet amyloid polypeptide (IAPP) identify critical species variants for fibrillization.. Amyloid 2015;22(3):194-202.
    doi: 10.3109/13506129.2015.1070824pubmed: 26300107google scholar: lookup
  55. van Rooijen BD, van Leijenhorst-Groener KA, Claessens MM, Subramaniam V. Tryptophan fluorescence reveals structural features of alpha-synuclein oligomers.. J Mol Biol 2009 Dec 18;394(5):826-33.
    doi: 10.1016/j.jmb.2009.10.021pubmed: 19837084google scholar: lookup
  56. Goodale L, Frank N, Hermida P, D'Oench S. Evaluation of a thyrotropin-releasing hormone solution stored at room temperature for pituitary pars intermedia dysfunction testing in horses.. Am J Vet Res 2015 May;76(5):437-44.
    doi: 10.2460/ajvr.76.5.437pubmed: 25909376google scholar: lookup

Citations

This article has been cited 13 times.
  1. Gołyński M, Metyk M, Ciszewska J, Szczepanik MP, Fitch G, Bęczkowski PM. Homocysteine-Potential Novel Diagnostic Indicator of Health and Disease in Horses. Animals (Basel) 2023 Apr 11;13(8).
    doi: 10.3390/ani13081311pubmed: 37106874google scholar: lookup
  2. Kirkwood NC, Hughes KJ, Stewart AJ. Prospective Case Series of Clinical Signs and Adrenocorticotrophin (ACTH) Concentrations in Seven Horses Transitioning to Pituitary Pars Intermedia Dysfunction (PPID). Vet Sci 2022 Oct 17;9(10).
    doi: 10.3390/vetsci9100572pubmed: 36288186google scholar: lookup
  3. Kirkwood NC, Hughes KJ, Stewart AJ. Pituitary Pars Intermedia Dysfunction (PPID) in Horses. Vet Sci 2022 Oct 10;9(10).
    doi: 10.3390/vetsci9100556pubmed: 36288169google scholar: lookup
  4. Christenson PR, Li M, Rowden G, Schwabenlander MD, Wolf TM, Oh SH, Larsen PA. A field-deployable diagnostic assay for the visual detection of misfolded prions. Sci Rep 2022 Jul 18;12(1):12246.
    doi: 10.1038/s41598-022-16323-ypubmed: 35851406google scholar: lookup
  5. Ademoye TA, Ganegamage SK, Masoudi B, Ibrahium OMH, Alnakhala H, Tripathi A, Dettmer U, Ostafe R, Borhan B, Fortin JS. In Vitro Evaluation of Amide-Linked Coumarin Scaffolds for the Inhibition of α‑Synuclein and Tau Aggregation. ACS Omega 2025 Sep 2;10(34):38498-38514.
    doi: 10.1021/acsomega.5c02435pubmed: 40918337google scholar: lookup
  6. Menzies-Gow NJ. Equine Pituitary Pars Intermedia Dysfunction. Vet Sci 2025 Aug 20;12(8).
    doi: 10.3390/vetsci12080780pubmed: 40872730google scholar: lookup
  7. Wang W, Gibson J, Horsman S, Mikkelsen D, Bertin FR. Characterization and comparison of fecal microbiota in horses with pituitary pars intermedia dysfunction and age-matched controls. J Vet Intern Med 2025 Jan-Feb;39(1):e17288.
    doi: 10.1111/jvim.17288pubmed: 39853825google scholar: lookup
  8. Elbatrawy AA, Ademoye TA, Alnakhala H, Tripathi A, Plascencia-Villa G, Zhu X, Perry G, Dettmer U, Fortin JS. Exploring the rhodanine universe: Design and synthesis of fluorescent rhodanine-based derivatives as anti-fibrillar and anti-oligomer agents against α-synuclein and 2N4R tau. Bioorg Med Chem 2024 Dec 15;116:117990.
    doi: 10.1016/j.bmc.2024.117990pubmed: 39550891google scholar: lookup
  9. Neufang L, Ramos J, Eda S, Flatland B, Giori L. Initial development of a rapid, portable, stall-side ELISA for the measurement of equine adrenocorticotropic hormone. J Vet Diagn Invest 2025 Jan;37(1):208-211.
    doi: 10.1177/10406387241285453pubmed: 39320416google scholar: lookup
  10. Horgan NG, McCarty AM, Hetak AA, Penticoff HB, Fortin JS. Understanding alpha-synuclein aggregation propensity in animals and humans. Biochem Biophys Rep 2024 Sep;39:101810.
    doi: 10.1016/j.bbrep.2024.101810pubmed: 39224226google scholar: lookup
  11. Ganegamage SK, Ramirez E, Alnakhala H, Tripathi A, Nguyen CCD, Zami A, Ostafe R, Tian S, Dettmer U, Fortin JS. 1,4-Diurea- and 1,4-Dithiourea-Substituted Aromatic Derivatives Selectively Inhibit α-Synuclein Oligomer Formation In Vitro. ACS Omega 2024 Jan 9;9(1):1216-1229.
    doi: 10.1021/acsomega.3c07453pubmed: 38222653google scholar: lookup
  12. Ramirez E, Ganegamage SK, Min S, Patel H, Ogunware A, Plascencia-Villa G, Alnakhala H, Shimanaka K, Tripathi A, Wang KW, Zhu X, Rochet JC, Kuo MH, Counts SE, Perry G, Dettmer U, Lasagna-Reeves CA, Fortin JS. Evaluation of N- and O-Linked Indole Triazines for a Dual Effect on α-Synuclein and Tau Aggregation. ACS Chem Neurosci 2023 Nov 1;14(21):3913-3927.
    doi: 10.1021/acschemneuro.3c00464pubmed: 37818657google scholar: lookup
  13. Ramirez E, Ganegamage SK, Elbatrawy AA, Alnakhala H, Shimanaka K, Tripathi A, Min S, Rochet JC, Dettmer U, Fortin JS. 5-Nitro-1,2-benzothiazol-3-amine and N-Ethyl-1-[(ethylcarbamoyl)(5-nitro-1,2-benzothiazol-3-yl)amino]formamide Modulate α-Synuclein and Tau Aggregation. ACS Omega 2023 Jun 6;8(22):20102-20115.
    doi: 10.1021/acsomega.3c02668pubmed: 37305264google scholar: lookup
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