Shank postsynaptic scaffolding proteins in autism spectrum disorder: mouse models and their dysfunctions in behaviors, synapses, and molecules
Open accessAbstract
Postsynaptic scaffolding proteins, which are major components of the postsynaptic density (PSD) at excitatory synapses, include Shank, PSD-95, A-kinase anchoring protein, Homer, and SAP90/PSD-95-associated protein families and play crucial roles in synaptic structure, signaling, and functions. Several genetic studies have indicated that postsynaptic scaffolding proteins contribute to the etiology of various psychiatric disorders, including neurodevelopmental disorders. Indeed, mice with mutations or deletions in specific genes encoding postsynaptic scaffolding proteins display alterations in behavioral phenotypes that are relevant to specific psychiatric disorders. Here, we review recent studies on various mutant mouse models of Shank postsynaptic scaffolding proteins associated with autism spectrum disorder, a major neurodevelopmental disorder, and discuss future directions and therapeutic strategies for the treatment of autism spectrum disorder.
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Disruption of SHANK family proteins alters PSD architecture, receptor localization, and subsequent signaling, leading to impaired synaptic transmission and plasticity that recapitulates autism-related phenotypes in animal models.
“Disruption of SHANK family proteins alters PSD architecture, receptor localization, and subsequent signaling (Bucher et al., 2021), leading to impaired synaptic transmission and plasticity that recapitulates autism-related phenotypes in animal models (Eltokhi et al., 2021; Jung and Park, 2022).”
From Biological hierarchy from genotype to phenotype in syndromic and non-syndromic autism spectrum disorder (2026) · cites this paper as Jung and Park, 2022
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Qing, Z., Yin, Z., Chen, B., Rao, Z., Yin, D., Li, D., Lu, Y., Shi, M., Li, S., Xu, Y., et al. (2026) · Frontiers in Neuroscience · doi:10.3389/fnins.2026.1964684
“Their disruption leads to widespread alterations in spine architecture and synaptic capacity across neuronal populations in ASD (Duncan et al., 2021; Jung and Park, 2022).”
- Authors
- Jung, S., & Park, M.
- Affiliations
- Korean Association Of Science and Technology Studies (KR)
- Corresponding author
- Park, Mikyoung
- Venue
- Pharmacological Research
- Publisher
- Elsevier BV
- Published
- 2022-08
- Volume
- 182
- Pages
- 106340
- ISSN
- 1043-6618 (ISSN-L)
- OpenAlex
- W4283776964
- Cited by
- 42
- References
- 15
- Citations by year
- 2026: 10 · 2025: 13 · 2024: 10 · 2023: 5 · 2022: 4
- FWCI
- 1.23
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Pharmacological Research (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Korea Institute of Science and Technology (2E31512)
- National Research Foundation of Korea
- Ministry of Science, ICT and Future Planning (NRF-2018M3C7A1021848, NRF-2021R1A2C2004606)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- shank, postsynaptic scaffolding proteins, autism spectrum disorder, postsynaptic density, PSD-95, A-kinase anchoring proteins, Homer, mouse model, neurodevelopmental disorders, synaptic dysfunction, behavioral phenotypes, mental illness, treatment options
- MeSH terms
- Autism Spectrum Disorder, Animals, Disease Models, Animal, Humans, Mutation, Nerve Tissue Proteins, Synapses, Mice
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