Neurexins, Ephrin receptors, and N-cadherin signaling as emerging mechanisms in synaptic dysfunction and neurodegenerative diseases

Synaptic cell adhesion molecules (SAMs) are essential for axon pathfinding and synaptic establishment during neurodevelopment, bridging the pre- and postsynaptic compartments across the synaptic cleft. While this function is well established, recent evidence has shown these proteins also exert key neuronal functions throughout the neuron’s life, regulating neuronal communication at mature synapses. Given these novel roles, SAMs are emerging as important elements relating to mental health and as significant contributors to age-related diseases, such as neurodegenerative disorders. For insight into this emerging role of SAMs, we focused on three pivotal regulator families of the central nervous system: Neurexins, Ephrin Receptors, and N-cadherins. This review summarizes the emerging roles of three pivotal cell adhesion families of the central nervous system in age-associated neurodegenerative disorders, highlighting new regulatory mechanisms at mature synapses.