Equine pituitary pars intermedia dysfunction: a spontaneous model of synucleinopathy

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...

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Bibliographic Details
Published in:Scientific reports 2021-08, Vol.11 (1), p.16036-16036, Article 16036
Main Authors: Fortin, Jessica S., Hetak, Ashley A., Duggan, Kelsey E., Burglass, Caroline M., Penticoff, Hailey B., Schott, Harold C.
Format: Article
Language:English
Subjects:
631/92/470/2284
639/766/930/328/2082
692/163/2743/2742/1738
692/699/375/365/1718
Endocrine disorders
Fibrils
Horses
Humanities and Social Sciences
Movement disorders
multidisciplinary
Neurodegenerative diseases
Parkinson's disease
Peptides
Pituitary
Protein seeding
Science
Science (multidisciplinary)
Synuclein
Transmission electron microscopy
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-021-95396-7