synaptopathies

Synaptopathies are disorders in which synapses—the functional contacts between neurons—are disrupted in number, structure, or function. The term encompasses a heterogeneous set of conditions, often genetic but also acquired, in which synaptic transmission and plasticity are perturbed. Pathogenesis may involve presynaptic vesicle release, postsynaptic receptor signaling, or the assembly of the postsynaptic density and adhesion molecules that couple neurons across the synaptic cleft.

Genetic synaptopathies include mutations in genes encoding synaptic scaffolds and adhesion molecules (for example SHANK3, a postsynaptic scaffolding protein linked to autism spectrum disorders; NRXN1, NRXN3 and NLGN3/4X neuroligin-neurexin adhesion partners; SYNGAP1, a regulator of AMPA receptor trafficking; STXBP1/Munc18-1, critical for neurotransmitter release). These disruptions can impair synapse formation, maturation, and plasticity, leading to neurodevelopmental phenotypes such as intellectual disability, autism, and epilepsy.

Acquired synaptopathies can follow traumatic brain injury, infections, autoimmune processes, or neurodegenerative diseases (for example synaptic loss and receptor dysfunction in Alzheimer's disease), often correlating with cognitive or behavioral symptoms.

Clinical and research implications focus on restoring synaptic function, targeting receptor trafficking, or modulating plasticity. Advances in imaging and genomics aid diagnosis, and potential therapies include pharmacological agents that enhance synaptic transmission or gene therapies for specific defects. See also synapse, neuroligin-neurexin adhesion, and synaptic plasticity.