Emerging Synaptic Molecules as Candidates in the Etiology of Neurological Disorders

Table 1

Presynaptic proteins involved in different synaptopathies and their role in physiological synaptic function.

	Function	Neurological disease	References
Synaptic vesicles proteins
Synapsin 1	Mobilization, release, and tethering of SV to the cytoskeleton away from the AZ	BPD	[23]
		Epilepsy	[24, 25]
		ASD	[25]
Synapsin 2	SVs mobilization and regulation of the number and density of the reserve pool	SCZ	[23, 26–30]
		Epilepsy	[31]
		BPD	[23, 32]
Synapsin 3	Synaptogenesis and modulation of neurotransmitter release	SCZ	[23, 33]
		BPD	[23]
Synaptophysin	Control of SVs endocytosis	SCZ	[34]
		BPD	[35]
Cytomatrix of active zone proteins
RIMs	Docking, SV fusion, and neurotransmitter release; Synaptic plasticity	SCZ; ASD	[36, 37]; [38, 39]
Piccolo	AZ scaffolding protein	SCZ	[37]
		MDD	[40–42]
		BPD	[43]
SNARE proteins
SNAP25	Mediation of vesicle docking and fusion	BPD	[35, 44, 45]
		SCZ	[44, 46, 47]
		ADHD	[48–50]
Adhesion molecules
SynCAM1	Synapse formation, synaptic plasticity, and axonal pathfinding	ASD	[51–54]
Cadherin	Selection of neuronal target, synapse formation, and plasticity	SCZ	[55, 56]
		BPD	[55]
		ASD	[55, 57–60]
		ADHD	[61]
NRXN1	Formation and maturation of the synapse	ASD	[62–65]
		SCZ	[66–68]

The table summarizes the physiological synaptic function of presynaptic proteins whose alterations result in synaptopathies related to neurodevelopmental, neuropsychiatric, and neurodegenerative diseases. ADHD, attention deficit hyperactivity disorder; ASD, autism spectrum disorder; AZ, active zone; BPD, bipolar disorder; MDD, major depressive disorder; NRXN, neurexin; RIM, Rab3a interacting molecule; SCZ, schizophrenia; SynCAMs, Synaptic adhesion molecules; SV, synaptic vesicle.