Equine pituitary pars intermedia dysfunction: a spontaneous model of synucleinopathy
Autor: | Ashley A. Hetak, Caroline M. Burglass, Harold C. Schott, Hailey B. Penticoff, Kelsey E. Duggan, Jessica S. Fortin |
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Rok vydání: | 2021 |
Předmět: |
medicine.medical_specialty
Aging Parkinson's disease Synucleinopathies Pituitary diseases Science animal diseases Biology Protein aggregation Fibril Article chemistry.chemical_compound Internal medicine medicine Pituitary pars intermedia dysfunction Animals Horses Pituitary Gland Intermediate Multidisciplinary Endocrine disease Pars intermedia medicine.disease Pathophysiology nervous system diseases Disease Models Animal Endocrinology chemistry nervous system alpha-Synuclein Medicine Thioflavin Horse Diseases Transmission electron microscopy |
Zdroj: | Scientific Reports Scientific Reports, Vol 11, Iss 1, Pp 1-11 (2021) |
ISSN: | 2045-2322 |
Popis: | 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. |
Databáze: | OpenAIRE |
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