ABSTRACT
Cell Death ........................................................................................ 177 8.3.2 Huntington’s Disease ....................................................................... 177 8.3.3 Alzheimer’s Disease ........................................................................ 179 8.3.4 Parkinson’s Disease ......................................................................... 179 8.3.5 Schizophrenia and Mood Disorders ................................................ 181 8.3.6 Other Disorders ................................................................................ 182
Acknowledgments .................................................................................................. 182 References .............................................................................................................. 182
At glutamatergic synapses, NMDA receptors (NMDARs) are localized with other ionotropic glutamate receptors [AMPA receptors (AMPARs) and kainate receptors] and with metabotropic glutamate receptors. Targeting the necessary number of NMDARs to the proper sites at synapses is critical for normal glutamatergic neurotransmission and synaptic plasticity. Additional diversity of NMDAR responses arises from the complexity of subunit composition and variations in localization. Thus, the mechanisms of NMDAR trafficking and targeting must address the complex needs of neurons. For
example, NMDARs must be transported to different subcellular sites because some receptors are localized to synaptic sites (pre-and postsynaptic) while others are localized extrasynaptically.1-4
NMDAR subunit expression differs as a function of brain region and developmental age.5-7 Subunit composition may determine subcellular localization, i.e., in adults, NR2A-containing receptors are enriched at synapses while extrasynaptic receptors are predominantly NR2B-containing complexes.1,2,4 Furthermore, evidence indicates the incorporation of more than one type of NR2 subunit in each complex (tri-heteromeric NR1/NR2X/NR2Y) such as NR1/NR2A/NR2B receptors in hippocampal neuron synapses, NR1/NR2A/NR2C in cerebellar granule cell synapses, and NR1/NR2B/NR2D in substantia nigra dopaminergic neurons.8 Finally, different NMDARs may be expressed at different synapses within the same neuron.4 Thus, the mechanisms of NMDAR trafficking must be varied and well regulated to meet the needs of neurons.
