Morphological remodeling of C. elegans neurons during aging is modified by compromised protein homeostasis

Npj Aging and Mechanisms of Disease
Elena M VayndorfBarbara E Taylor

Abstract

Understanding cellular outcomes, such as neuronal remodeling, that are common to both healthy and diseased aging brains is essential to the development of successful brain aging strategies. Here, we used Caenorhabdits elegans to investigate how the expression of proteotoxic triggers, such as polyglutamine (polyQ)-expanded huntingtin and silencing of proteostasis regulators, such as the ubiquitin-proteasome system (UPS) and protein clearance components, may impact the morphological remodeling of individual neurons as animals age. We examined the effects of disrupted proteostasis on the integrity of neuronal cytoarchitecture by imaging a transgenic C. elegans strain in which touch receptor neurons express the first 57 amino acids of the human huntingtin (Htt) gene with expanded polyQs (128Q) and by using neuron-targeted RNA interference in adult wild-type neurons to knockdown genes encoding proteins involved in proteostasis. We found that proteostatic challenges conferred by polyQ-expanded Htt and knockdown of specific genes involved in protein homeostasis can lead to morphological changes that are restricted to specific domains of specific neurons. The age-associated branching of PLM neurons is suppressed by N-ter polyQ-expanded...Continue Reading

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Related Concepts

Calcinus elegans
Cyartonema elegans
Coleonyx elegans
Biochemical Pathway
Proteasome Pathway
Cestrum elegans
Strategy
Clarkia unguiculata
Clathrulina elegans
Gene Knockdown Techniques

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