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...

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Autores principales:	Jessica S. Fortin, Ashley A. Hetak, Kelsey E. Duggan, Caroline M. Burglass, Hailey B. Penticoff, Harold C. Schott
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/31b331f9eae4475cb801f4fb07245979
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spelling	oai:doaj.org-article:31b331f9eae4475cb801f4fb072459792021-12-02T18:49:34ZEquine pituitary pars intermedia dysfunction: a spontaneous model of synucleinopathy10.1038/s41598-021-95396-72045-2322https://doaj.org/article/31b331f9eae4475cb801f4fb072459792021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95396-7https://doaj.org/toc/2045-2322Abstract 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.Jessica S. FortinAshley A. HetakKelsey E. DugganCaroline M. BurglassHailey B. PenticoffHarold C. SchottNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jessica S. Fortin Ashley A. Hetak Kelsey E. Duggan Caroline M. Burglass Hailey B. Penticoff Harold C. Schott Equine pituitary pars intermedia dysfunction: a spontaneous model of synucleinopathy
description	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.
format	article
author	Jessica S. Fortin Ashley A. Hetak Kelsey E. Duggan Caroline M. Burglass Hailey B. Penticoff Harold C. Schott
author_facet	Jessica S. Fortin Ashley A. Hetak Kelsey E. Duggan Caroline M. Burglass Hailey B. Penticoff Harold C. Schott
author_sort	Jessica S. Fortin
title	Equine pituitary pars intermedia dysfunction: a spontaneous model of synucleinopathy
title_short	Equine pituitary pars intermedia dysfunction: a spontaneous model of synucleinopathy
title_full	Equine pituitary pars intermedia dysfunction: a spontaneous model of synucleinopathy
title_fullStr	Equine pituitary pars intermedia dysfunction: a spontaneous model of synucleinopathy
title_full_unstemmed	Equine pituitary pars intermedia dysfunction: a spontaneous model of synucleinopathy
title_sort	equine pituitary pars intermedia dysfunction: a spontaneous model of synucleinopathy
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/31b331f9eae4475cb801f4fb07245979
work_keys_str_mv	AT jessicasfortin equinepituitaryparsintermediadysfunctionaspontaneousmodelofsynucleinopathy AT ashleyahetak equinepituitaryparsintermediadysfunctionaspontaneousmodelofsynucleinopathy AT kelseyeduggan equinepituitaryparsintermediadysfunctionaspontaneousmodelofsynucleinopathy AT carolinemburglass equinepituitaryparsintermediadysfunctionaspontaneousmodelofsynucleinopathy AT haileybpenticoff equinepituitaryparsintermediadysfunctionaspontaneousmodelofsynucleinopathy AT haroldcschott equinepituitaryparsintermediadysfunctionaspontaneousmodelofsynucleinopathy
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Equine pituitary pars intermedia dysfunction: a spontaneous model of synucleinopathy

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