New mechanism regulating synapse loss in Alzheimer’s discovered

In the brain, the connections between neurons, called synapses, are continuously monitored and remodelled: the elimination of damaged or no longer functional synapses is an essential process for maintaining the balance of neuronal networks. This function is carried out mainly by microglia, the brain’s resident immune cells. Much less is known, however, about the contribution of other glial cells, such as astrocytes, especially when these mechanisms become altered in neurodegenerative diseases.

Thanks to STARS (Supporting Talent in ReSearch) funding from the University of Padua, Laura Civiero, lecturer in the Department of Biology of the University of Padua (who recently obtained funding from the Michael J. Fox Foundation to develop innovative therapeutic strategies for the benefit of people affected by Parkinson’s disease) has launched and strengthened a new line of research dedicated precisely to the study of glia, a group of cells that are fundamental to brain function. For a long time considered merely support cells for neurons, glial cells are now recognised as active protagonists in the health of the nervous system and in neurodegenerative diseases.

The research carried out focused on understanding how astrocytes participate in the control and removal of synapses and how this process contributes to the loss of nerve connections in Alzheimer’s disease. The study identified a new mechanism through which astrocytes recognise and remove altered synapses: the results were published in the scientific journal «Molecular Neurodegeneration» in the article Atypical chemokine receptor 3 regulates synaptic removal in disease astrocytes.

«In the brain, synapses are continuously monitored to ensure that neuronal networks function correctly. When a synapse becomes damaged or no longer functional, it must be recognised and eliminated. Our study shows that, in Alzheimer’s disease, astrocytes can contribute to this process through the ACKR3 receptor – comments Laura Civiero, first author of the article –. This receptor acts as a sort of molecular sensor: it recognises a signal present on altered synapses and guides astrocytes towards their removal. However, when this mechanism is excessively active, it can contribute to the pathological loss of neuronal connections. Reducing ACKR3 activity in experimental models made it possible to protect synapses and improve some aspects of cognitive function».

These results open up new perspectives in the study of neurodegeneration: understanding the role of astrocytes more fully means looking beyond the neuron and considering the brain as a complex system, in which different cell populations collaborate to maintain its function. Glia thus emerges as a possible target for future therapeutic strategies aimed at protecting neuronal connections and slowing the progression of neurodegenerative diseases.