Table 2.
Postsynaptic proteins involved in different synaptopathies and their role in physiological synaptic function.
| Protein | Function | Neurological disease | References |
|---|---|---|---|
| Adhesion molecules | |||
|
| |||
| NL1 | Memory formation and maturation of excitatory synapses | ASD | [111, 112] |
| AD | [113] | ||
| FXS | [114] | ||
|
| |||
| NL2 | Formation and remodeling of inhibitory synapses | SCZ | [115] |
| ASD | [116] | ||
|
| |||
| NL3 | Formation and remodeling of excitatory and inhibitory synapses | ASD | [105, 117–121] |
|
| |||
| NL4 | Formation and remodeling of excitatory and inhibitory synapses | ASD | [117–119, 122–126] |
|
| |||
| Glutamate receptors | |||
|
| |||
| NMDARs | Regulation of synaptic plasticity and memory formation | ASD | [127–129] |
| SCZ | [127, 130, 131] | ||
| AD | [132–136] | ||
| HD | [137, 138] | ||
|
| |||
| KARs | Maturation of neural circuits during development | ASD | [139–141] |
| SCZ | [142] | ||
| BPD | [142, 143] | ||
|
| |||
| AMPARs | Mediators of excitatory transmission and synaptic plasticity | ASD | [144] |
| SCZ | [145–147] | ||
| BPD | [148] | ||
| MDD | [149] | ||
| FXS | [150, 151] | ||
| HD | [152] | ||
|
| |||
| mGluRs | Regulation of neuronal excitability, learning, and memory | ASD | [153–156] |
| ID | [156] | ||
| FXS | [157–159] | ||
|
| |||
| Scaffolding proteins | |||
|
| |||
| PSD-95 | Stabilization of the synapse, and regulation of synaptic strength, transmission, and plasticity | AD | [160–162] |
| ASD | [163, 164] | ||
| SCZ | [164, 165] | ||
| HD | [166–168] | ||
| FXS | [169–173] | ||
|
| |||
| Shank1 | Regulation of the structural and functional organization of the dendritic spines | ASD | [174–176] |
| SCZ | [177, 178] | ||
|
| |||
| Shank2 | Synaptogenesis; regulation of the molecular structure and modulation of interacting proteins in the PSD | ASD | [179–182] |
| ID | [183, 184] | ||
| SCZ | [185] | ||
|
| |||
| Shank3 | Synapse formation, dendritic spine maturation, and synaptic plasticity |
ASD | [186–193] |
| PMS | [194–196] | ||
| SCZ | [197] | ||
|
| |||
| Homer | Organization, stabilization and function of the PSD, and contribution in dendritic spine morphogenesis | SCZ | [198–202] |
|
| |||
| SynGAP | Involvement in the cognitive development and synaptic transmission and function | SCZ | [203] |
| ASD | [204, 205] | ||
| ID | [206] | ||
|
| |||
| Gephyrin | Clustering and localization of glycine and GABA receptors at inhibitory synapses | ASD | [207] |
| SCZ | |||
| Epilepsy | [208] | ||
|
| |||
| Other postsynaptic-associated proteins | |||
|
| |||
| DISC1 | Regulation of synaptic plasticity | SCZ | [209–212] |
| Depression | [209, 213] | ||
| BPD | [210] | ||
| ASD | [214] | ||
| AD | [215] | ||
The table summarizes the physiological synaptic function of postsynaptic proteins whose alterations result in synaptopathies related to neurodevelopmental, neuropsychiatric, and neurodegenerative diseases. AD, Alzheimer's disease; AMPARs, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; BPD, bipolar spectrum disorder; ASD, autism spectrum disorder; DISC1, disrupted in schizophrenia 1; FXS, Fragile X syndrome; HD, Huntington's Disease; ID, intellectual disability; KARs, kainate receptors; MDD, major depressive disorder; mGluRs, metabotropic glutamate receptors; NLs, neuroligins; NMDARs, N-methyl-D-aspartate; PMS, Phelan-McDermid syndrome; PSD-95, postsynaptic density-95; SCZ, schizophrenia.