Nlg4y

Genes are listed according to their priority of testing. All of these genes are expressed in the brain. DLG4 and DLG2 encode two members of the membrane-associated guanylate kinase (MAGUK) family. These two MAGUK proteins regulate clustering of receptors, ion channels, and associated signalling proteins.

Thus, mechanisms that govern assembly of neuroligins and their synaptic partners may be critical for controlling neuronal excitability. Worth mentioning, PSD-95 association with the PSD is dynamic and is regulated by synaptic activity and palmitate cycling on PSD-9568. Moreover, synaptic activity upregulates PSD-95 expression through a neuregulin mediated pathway69. In contrast, administration of cocaine, a drug known to cause hyperexcitability, results in downregulation of PSD-95 in the striatum70. Finally, mutation of FMR1 gene results in a loss of regulation of PSD-95 expression71. Thus, chromosomal aberrations or defects in pathways that control the expression of PSD-95 and neuroligins may induce profound effects on synaptic balance and disturb processes that influence memory and behaviour. However, further studies are required to address whether alteration in the expression of these proteins indeed results in altered E/I synaptic ratio and in the manifestation of abnormal behaviour associated with autism. Treatment with peptides that interfere with coupling of neuroligins with their synaptic partners that regulate their retention at the synapse may offer a new tool for manipulating the disturbed E/I ratio associated with brain disorders such as autism.

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