Genetic reduction of tyramine β hydroxylase suppresses Tau toxicity in a Drosophila model of tauopathy

NEUROSCIENCE LETTERS

卷:755

Article

Nangia, Varuna¹  O'Connell, Julia¹  Chopra, Kusha¹  Qing, Yaling¹  Reppert, Camille¹  Chai, Cynthia M.¹  Bhasiin, Kesshni¹  Colodner, Kenneth J.¹ 

[1] Mt Holyoke Coll, Program Neurosci & Behav, 118 Clapp Lab, S Hadley, MA 01075 USA

关键词: Tau;    Tauopathies;    tah;    Octopamine;    Drosophila;   

DOI  :  10.1016/j.neulet.2021.135937

来源: Elsevier

【 摘 要 】

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 beta hydroxylase (t beta h), 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 t beta h suppresses Tau toxicity, independent of Tau phosphorylation. These findings show that reduction of t beta h, 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.

【 授权许可】

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