Fig. 2: Synapse-restoring potential of Cbln1 and synthetic synaptic organizer CPTX across neurological disease models.
From: GluD1 at the synaptic crossroads: from domain structure to circuit dysfunction
The top panels depict the molecular mechanism underlying synaptic restoration. On the left, under pathological conditions such as chronic pain, Alzheimer’s disease, ataxia, and spinal cord injury, there in synaptic destabilization. On the right, the exogenous administration of Cbln1 or CPTX reestablishes transsynaptic signaling by bridging presynaptic neurexins and postsynaptic GluD1 or AMPA receptors, thereby restoring synaptic integrity. The bottom panels illustrate the therapeutic outcomes observed across various disease models. Before the injection of Cbln1/CPTX, animals exhibit behavioral and structural deficits associated with chronic pain, neurodegeneration, motor dysfunction, and neural injury. Following the injection, synaptic restoration is correlated with improved neuronal structure, behavioral recovery, and functional circuit repair. These findings underscore the translational potential of targeting extracellular scaffolds such as Cbln1 and synthetic organizers like CPTX for the restoration of circuit function in a range of neurological disorders.
