Emerging Synaptic Molecules as Candidates in the Etiology of Neurological Disorders

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.