1. Dendrite injury triggers neuroprotection in Drosophila models of neurodegenerative disease.
- Author
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Prange SE, Bhakta IN, Sysoeva D, Jean GE, Madisetti A, Le HHN, Duong LU, Hwu PT, Melton JG, and Thompson-Peer KL
- Subjects
- Animals, Drosophila, Drosophila melanogaster, Peptides metabolism, Neurons metabolism, Neurons pathology, Dendrites metabolism, Dendrites pathology, Neurodegenerative Diseases metabolism, Neurodegenerative Diseases pathology, Neurodegenerative Diseases genetics, Disease Models, Animal, Neuroprotection
- Abstract
Dendrite defects and loss are early cellular alterations observed across neurodegenerative diseases that play a role in early disease pathogenesis. Dendrite degeneration can be modeled by expressing pathogenic polyglutamine disease transgenes in Drosophila neurons in vivo. Here, we show that we can protect against dendrite loss in neurons modeling neurodegenerative polyglutamine diseases through injury to a single primary dendrite branch. We find that this neuroprotection is specific to injury-induced activation of dendrite regeneration: neither injury to the axon nor injury just to surrounding tissues induces this response. We show that the mechanism of this regenerative response is stabilization of the actin (but not microtubule) cytoskeleton. We also demonstrate that this regenerative response may extend to other neurodegenerative diseases. Together, we provide evidence that activating dendrite regeneration pathways has the potential to slow-or even reverse-dendrite loss in neurodegenerative disease., (© 2024. The Author(s).)
- Published
- 2024
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