AMPA receptors targeting

Gerges NZ, Backos DS, Rupasinghe CN, Spaller MR, Esteban JA. 2006. Dual role of the exocyst in AMPA receptor targeting and insertion into the postsynaptic membrane. EMBO J 25 1623-1634. 

Chen CC, Lamping KG, Nuno DW, Barresi R, Prouty SJ, Lavoie JL, Cribbs LL, England SK, Sigmund CD, Weiss RM, Williamson RA, Hill JA, Campbell KP (2003) Abnormal coronary function in mice deficient in alphalH T-type Ca2+ channels. Science 302 1416-8 Chen L, Chetkovich DM, Petralia RS, Sweeney NT, Kawasaki Y, Wenthold RJ, Bredt DS, Nicoll RA (2000) Stargazin regulates synaptic targeting of AMPA receptors by two distinct mechanisms. Nature 408 936 13... 

Because AMPA receptors function in concert with NMDA receptors, they have been proposed as alternative therapeutic targets in schizophrenia. AMPAkines function as positive allosteric modulators of AMPA receptor-mediated neurotransmission, and facilitate learning and memory in both human (Ingvar et al., 1997) and animal (Hampson et al., 1998) models. Further, these drugs act synergistically with antipsycho-tics to reverse amphetamine-induced hyperactivity (Johnson et al., 1999). 

O Neill MJ, Bleakman D, Zimmerman DM, Nisenbaum ES (2004) AMPA receptor potentiators for the treatment of CNS disorders. Curr Drug Targets CNS Neurol Disord 3 181-194. 

Chen L, Chetkovich DM, Petralia RS, Sweeney NT, Kawasaki Y, et al. 2000. Stargazin regulates synaptic targeting of AMPA receptors by two distinct mechanisms. Nature 408 936 43... 

Perez, J.L., Khatri, L., Chang, C., Srivastava, S., Osten, P., Ziff, E.B. PICK1 targets activated protein kinase calpha to AMPA receptor clusters in spines of hippocampal neurons and reduces surface levels of the AMPA-type glutamate receptor subunit 2. J. Neurosci. 2001, 21, 5417-28. 

Jayakar, S.S. and Dikshit, M., 2004. AMPA receptor regulation mechanisms future target for safe neuroprotective drugs, Int. J. Neurosci., 114, pp. 695-734. 

O Neill, M. J., Witkin, J. M. AMPA receptor potentiators application for depression and Parkinson s disease. Curr. Drug Targets 2007, 8, 603-620. 

Like NMDA receptors, AMPA receptors are also typically concentrated at postsynaptic sites of excitatory synapses. Recent evidence suggests, however, that the targeting of AMPA receptors to synapses is much more heterogeneous than that of NMDA receptors. Many excitatory synapses contain NMDA receptors but not AMPA receptors, especially early in development, and the content of AMPA receptors in AMPA receptor-positive synapses is quite variable (Nusser et al., 1998 Petralia et al., 1999 Takumi et al., 1999). Such morphologically silent... 

Ap-mediated activation of calcineurin, resulting in dephosphorylation and activation of STEP [191], and (2) Ap-inhibition of the protea-some, resulting in decreased degradation of STEP [197]. As a result, STEP activity is increased in AD, leading to loss of NMDA and AMPA receptors from synaptosomal membranes. Collectively, these studies suggest that inhibition of STEP activity may be beneficial in AD treatment, and validate STEP as a novel drug target in AD (and perhaps other neuropsychiatric disorders, reviewed in ref 131). 

Rogawski MA, Donevan SD (1999) AMPA receptors in epilepsy and as targets for antiepileptic drugs. Adv Neurol 79 947-963... 

---