Genetic reduction of tyramine ß hydroxylase suppresses Tau toxicity in a Drosophila model of tauopathy.
Neurosci Lett
; 755: 135937, 2021 06 11.
Article
en En
| MEDLINE
| ID: mdl-33910059
Tauopathies are a class of neurodegenerative diseases characterized by the abnormal phosphorylation and accumulation of the microtubule-associated protein, Tau. These diseases are associated with degeneration and dysfunction of the noradrenergic system, a critical regulator of memory, locomotion, and the fight or flight response. Though Tau pathology accumulates early in noradrenergic neurons, the relationship between noradrenaline signaling and tauopathy pathogenesis remains unclear. The fruit fly, Drosophila melanogaster, is a valuable model organism commonly used to investigate factors that promote Tau-mediated degeneration. Moreover, Drosophila contain the biogenic amine, octopamine, which is the functional homolog to noradrenaline. Using a Drosophila model of tauopathy, we conducted a candidate modifier screen targeting tyramine ß hydroxylase (tßh), the enzyme that controls the production of octopamine in the fly, to determine if levels of this enzyme modulate Tau-induced degeneration in the fly eye. We found that genetic reduction of tßh suppresses Tau toxicity, independent of Tau phosphorylation. These findings show that reduction of tßh, a critical enzyme in the octopaminergic pathway, suppresses Tau pathogenicity and establishes an interaction that can be further utilized to determine the relationship between noradrenergic-like signaling and Tau toxicity in Drosophila.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas tau
/
Tauopatías
/
Oxigenasas de Función Mixta
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Neurosci Lett
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Irlanda