The project, entitled “Astrocyte dysfunctions in Phelan-McDermid syndrome: from mechanisms towards new therapeutic strategies (SHANKAstro)”, is led by João Peça, professor at the Faculty of Science and Technology of the University of Coimbra (FCTUC) and researcher at the Center for Neuroscience and Cell Biology (CNC), with the participation of scientists from Germany, Belgium, Italy and Switzerland.
The major goal of the three-year research is to understand which brain cells play a major role in autism, and in particular how mutations in the SHANK3 gene impact normal function during the pathophysiology of the disease.
João Peça explains that mutations in the SHANK3 gene “are one of the most common causes diagnosed for autism. However, surprisingly, little is known about the consequences of mutations in this gene. Since its original discovery, mutations in SHANK3 have been most commonly studied in neurons.”
However, he stresses, “Recent evidence suggests that astrocytes, somewhat neglected brain cells, may also play a key role in the development of autism. Astrocytes provide critical metabolic and trophic support for neurons and have recently been identified as “key actors” in the formation and maturation of neuronal circuits. Therefore, the dysfunction of astrocytes, resulting from the mutation in the SHANK3 gene, can lead to problems in the formation and maturation of the neuronal circuit, which will eventually lead to behavioral and cognitive abnormalities”.
In this study, which brings together several experts in the field of the SHANK3 gene and the astrocytes-biology, innovative models will be used, including genetically modified mouse models, as well as human brain organoids capable of closely mimicking human cell physiology.
If scientists manage to decipher the impact that the mutations in the SHANK3 gene have on autism, it will be possible to “discover and design successful therapies for neurodevelopmental diseases”, concludes João Peça.ERA-NET NEURON is a European funding network for research in Neuroscience, focused on brain diseases and nervous system disorders.