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How Is Neuronal Garbage Processed?

How Is Neuronal Garbage Processed?

Image credit: Arnold et al. 2018 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5789552/)

By Jamila Ahmed on Jul 30, 2020

How is neuronal garbage processed in humans?

Research on neuronal garbage processing has mostly been conducted in C. elegans and some murine cells. Many aspects of the neuronal garbage removal process are yet to be elucidated. In Melentijevic’s study, C. elegans neurons expelled a large vesicle which was later named as an exopher. The exopher may sound like an exosome but it certainly is not. On average the exophers were 4uM, thus exosomes are significantly smaller than exophers. Exophers are able to remove protein aggregates, lysosomes, and even [1]mitochondria.

There are many questions that still need to be answered

  1. What is the specific mechanism in which the trash is recognized?
  2. What is the exact mechanism of ejection from the cell?
  3. Where does the trash go and how is it degraded in mice and human cells?

Plaque-like structures are able to form from exophers carrying amyloid-beta. This information can provide insight into neurological disease progression that can be characterised with amyloid plaque, ghost tangles, and Lewy body [2]formation.

References

[1] Melentijevic, Ilija, et al. "C. elegans neurons jettison protein aggregates and mitochondria under neurotoxic stress." Nature, 542.7641, 2017, pp. 367-371.

[2] Fu, Hualin, et al. "Metabolic wastes are removed by excretosomes, nanotubes and exophers in mouse HT22 cells through an autophagic vesicle clustering mechanism." bioRxiv, 2019, pp. 699405.

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