Axon Injury-Induced Autophagy Activation Is Impaired in a C. elegans Model of Tauopathy.

International Journal of Molecular Sciences
Su-Hyuk KoLizhen Chen

Abstract

Autophagy is a conserved pathway that plays a key role in cell homeostasis in normal settings, as well as abnormal and stress conditions. Autophagy dysfunction is found in various neurodegenerative diseases, although it remains unclear whether autophagy impairment is a contributor or consequence of neurodegeneration. Axonal injury is an acute neuronal stress that triggers autophagic responses in an age-dependent manner. In this study, we investigate the injury-triggered autophagy response in a C. elegans model of tauopathy. We found that transgenic expression of pro-aggregant Tau, but not the anti-aggregant Tau, abolished axon injury-induced autophagy activation, resulting in a reduced axon regeneration capacity. Furthermore, axonal trafficking of autophagic vesicles were significantly reduced in the animals expressing pro-aggregant F3ΔK280 Tau, indicating that Tau aggregation impairs autophagy regulation. Importantly, the reduced number of total or trafficking autophagic vesicles in the tauopathy model was not restored by the autophagy activator rapamycin. Loss of PTL-1, the sole Tau homologue in C. elegans, also led to impaired injury-induced autophagy activation, but with an increased basal level of autophagic vesicles. Ther...Continue Reading

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Citations

Apr 4, 2021·Cells·Georgios Konstantinidis, Nektarios Tavernarakis

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Methods Mentioned

BETA
Transgenic
gene knockout
genotyping
PCR

Software Mentioned

Kymograph
Kymographs
GraphPad PRiSM

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