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Trends Cell Biol. 2011 Oct;21(10):594-603. doi: 10.1016/j.tcb.2011.07.003. Epub 2011 Aug 15.

Postsynaptic ProSAP/Shank scaffolds in the cross-hair of synaptopathies.

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Institute for Anatomy and Cell Biology, Ulm University, Ulm, Germany.


Intact synaptic homeostasis is a fundamental prerequisite for a healthy brain. Thus, it is not surprising that altered synaptic morphology and function are involved in the molecular pathogenesis of so-called synaptopathies including autism, schizophrenia (SCZ) and Alzheimer's disease (AD). Intriguingly, various recent studies revealed a crucial role of postsynaptic ProSAP/Shank scaffold proteins in all of the aforementioned disorders. Considering these findings, we follow the hypothesis that ProSAP/Shank proteins are key regulators of synaptic development and plasticity with clear-cut isoform-specific roles. We thus propose a model where ProSAP/Shank proteins are in the center of a postsynaptic signaling pathway that is disrupted in several neuropsychiatric disorders.

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