A common cause of synaptopathy is glutamate excitotoxicity. As shown in the animation, the over-activation of NMDA receptors leads to an increase in free intracellular calcium, which produces oxygen free-radicals and eventually neuronal dysfunction.[1]
Another example of synaptopathy occurs in the auditory system. This cochlear synaptopathy has been seen after prolonged noise exposure in both primate and non-primate models.[2][3] Two possible reasons for this neuronal death are both glutamate-mediated excitotoxicity in the postsynaptic terminal, and presynaptic ribbon damage which occurs by an unknown mechanism.[4]
Synaptopathies are attracting research interest because they provide an insight into fundamental mechanisms of synaptic transmission and because an improved understanding of disease mechanisms may lead to new treatments.
Some diseases of unknown etiology have been proposed to be synaptopathies. Examples include autism spectrum disorder[5] and schizophrenia.[6] Synaptic dysfunction can also occur in neurodegenerative disorders such as Alzheimer's.[7] Immune-mediated cerebellar ataxias represent a group of disorders causing cerebellar ataxia induced by a dysfunction of synapses.[8] Increasing knowledge of the genetic basis of these diseases has linked proteins to the function of the synapse. Age-related cochlear synaptic and neural degeneration has also been demonstrated in mice.[9]
Molecules such as FMRP1 act as translational repressor thus when ablated such as in FXS result in varying degrees of cellular and behavioural abnormalities. Additional molecules thought to be involved include SynGAP and SHANK1.[10]