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Genet."},{"key":"10.1016\/j.tins.2010.08.002_bib0450","doi-asserted-by":"crossref","first-page":"3254","DOI":"10.1093\/emboj\/cdg334","article-title":"Disruption of the endocytic protein HIP1 results in neurological deficits and decreased AMPA receptor trafficking","volume":"22","author":"Metzler","year":"2003","journal-title":"EMBO J."},{"key":"10.1016\/j.tins.2010.08.002_bib0455","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.neuron.2005.08.016","article-title":"The synaptic localization of NR2B-containing NMDA receptors Is controlled by interactions with PDZ proteins and AP-2","volume":"47","author":"Prybylowski","year":"2005","journal-title":"Neuron"},{"key":"10.1016\/j.tins.2010.08.002_bib0460","doi-asserted-by":"crossref","first-page":"12736","DOI":"10.1073\/pnas.0401860101","article-title":"Huntingtin-associated protein 1 regulates inhibitory synaptic transmission by modulating gamma-aminobutyric acid type A receptor membrane trafficking","volume":"101","author":"Kittler","year":"2004","journal-title":"Proc. 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Neurosci."},{"key":"10.1016\/j.tins.2010.08.002_bib0520","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.brainres.2006.08.035","article-title":"Memantine reduces striatal cell death with decreasing calpain level in 3-nitropropionic model of Huntington's disease","volume":"1118","author":"Lee","year":"2006","journal-title":"Brain Res."},{"key":"10.1016\/j.tins.2010.08.002_bib0525","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1002\/jnr.22239","article-title":"3-nitropropionic acid-induced mitochondrial permeability transition: comparative study of mitochondria from different tissues and brain regions","volume":"88","author":"Mirandola","year":"2010","journal-title":"J. Neurosci. 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