How brain cells recycle themselves

Neurons, marked in red and green, constantly recycle toxic protein aggregates, c
Neurons, marked in red and green, constantly recycle toxic protein aggregates, colored in light blue, by autophagy Vassiliki Nikoletopoulou Lab
A study published on June 5, 2023 in Neuron by a team from the University of Lausanne lifts part of the veil on the autophagy mechanism in neurons and glial cells.

Autophagy is an essential process in cellular life: it cleans up the waste produced by the cell’s machinery, eliminating useless, defective or toxic components, and recycling those that can be. This small internal reprocessing plant then provides the cell with a raw material that can be used to renew its constituents, such as proteins and organelles.

But when this mechanism goes wrong, when autophagy malfunctions, problems arise. Within brain cells, in neurons and glia, mutations in autophagy genes are linked to certain serious neurodevelopmental disorders, such as autism or epilepsy, or predispose to the development of neurodegenerative diseases later in life, such as Alzheimer’s or Parkinson’s.

How autophagy works - First of all, the waste products are enclosed in a kind of small sac, called an autophagic vesicle or autophagosome, which then merges with the lysosome, another enzyme-filled sac: this is where the various residues - proteins, sugars, lipids, genetic material - are degraded into their primary constituents, building blocks that are then reused by the cell. But when autophagy is impaired, neurons and other brain cells accumulate damaged proteins and organelles that clutter up their space and function.

Although the importance of autophagy for the brain’s physical shape has been demonstrated, until now it was not known what types of molecules and organelles were recycled by this mechanism.

The findings of a team from Lausanne

This is where the work of a team from the Department of Basic Neuroscience at the Faculty of Biology and Medicine (FBM) at the University of Lausanne comes in: We have developed a new method for purifying autophagic vesicles from mouse brains and analyzed the ’cargo’ they contain", explains Emmanouela Kallergi , first author of a study published today in Neuron and carried out in collaboration with Joern Dengjel’s group at the University of Fribourg. The scientists discovered that in neurons and glial cells of the brain, autophagy constantly recycles proteins that aggregate at the risk of causing disease, as well as organelles such as mitochondria, the power plants of cellular machinery. In addition, autophagy reprocesses a large number of synaptic proteins, essential for the transmission of activity between neurons.

’ We also demonstrate that the type of cerebral autophagic ’cargo’ changes dynamically in adolescence, as the brain matures, and in old age, adapting to the needs of each stage of life ’, adds Emmanouela Kallergi. ’ This information is very important for developing targeted therapeutic strategies that can promote the recycling of specific cellular elements, adapted to the needs of different diseases ’, comments group leader Vassiliki Nikoletopoulou , assistant professor at FBM and last author of the article published in Neuron.