In multicellular organisms, neurons integrate a diverse array of external cues to affect downstream changes in organismal health. Specifically, activation of the endoplasmic reticulum (ER) unfolded protein response (UPR) in neurons increases lifespan by preventing age-onset loss of ER proteostasis and driving lipid depletion in a cell non-autonomous manner. The mechanism of this communication is dependent on the release of small clear vesicles from neurons. We find dopaminergic neurons are necessary and sufficient for activation of cell non-autonomous UPR to drive lipid depletion in peripheral tissues, whereas serotonergic neurons are sufficient to drive protein homeostasis in peripheral tissues. These signaling modalities are unique and independent and together coordinate the beneficial effects of neuronal cell non-autonomous ER stress signaling upon health and longevity.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8820220PMC
http://dx.doi.org/10.1016/j.celrep.2020.108489DOI Listing

Publication Analysis

Top Keywords

cell non-autonomous
12
non-autonomous upr
8
dopaminergic neurons
8
lipid depletion
8
neurons sufficient
8
peripheral tissues
8
neurons
6
divergent nodes
4
non-autonomous
4
nodes non-autonomous
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!