{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T04:52:59Z","timestamp":1791089579883,"version":"4.1.0"},"reference-count":48,"publisher":"Society for Neuroscience","issue":"45","license":[{"start":{"date-parts":[[2007,5,8]],"date-time":"2007-05-08T00:00:00Z","timestamp":1178582400000},"content-version":"vor","delay-in-days":181,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2006,11,8]]},"abstract":"<jats:p>Amyotrophic lateral sclerosis (ALS), the most common adult-onset motor neuron disease is caused by a selective loss of motor neurons. One form of juvenile onset autosomal recessive ALS (ALS2) has been linked to the loss of function of the<jats:italic>ALS2<\/jats:italic>gene. The pathogenic mechanism of<jats:italic>ALS2<\/jats:italic>-deficiency, however, remains unclear. To further understand the function of alsin that is encoded by the full-length<jats:italic>ALS2<\/jats:italic>gene, we screened proteins interacting with alsin. Here, we report that alsin interacted with glutamate receptor interacting protein 1 (GRIP1) both<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>, and colocalized with GRIP1 in neurons. In support of the physiological interaction between alsin and GRIP1, the subcellular distribution of GRIP1 was altered in<jats:italic>ALS2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>spinal motor neurons, which correlates with a significant reduction of AMPA-type glutamate receptor subunit 2 (GluR2) at the synaptic\/cell surface of<jats:italic>ALS2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>neurons. The decrease of calcium-impermeable GluR2-containing AMPA receptors at the cell\/synaptic surface rendered<jats:italic>ALS2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>neurons more susceptible to glutamate receptor-mediated neurotoxicity. Our findings reveal a novel function of alsin in AMPA receptor trafficking and provide a novel pathogenic link between<jats:italic>ALS2<\/jats:italic>-deficiency and motor neuron degeneration, suggesting a protective role of alsin in maintaining the survival of motor neurons.<\/jats:p>","DOI":"10.1523\/jneurosci.2084-06.2006","type":"journal-article","created":{"date-parts":[[2006,11,8]],"date-time":"2006-11-08T17:18:09Z","timestamp":1163006289000},"page":"11798-11806","source":"Crossref","is-referenced-by-count":78,"title":["Amyotrophic Lateral Sclerosis 2-Deficiency Leads to Neuronal Degeneration in Amyotrophic Lateral Sclerosis through Altered AMPA Receptor Trafficking"],"prefix":"10.1523","volume":"26","author":[{"given":"Chen","family":"Lai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengsong","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie G.","family":"McCormack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsueh-Cheng","family":"Chiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta K.","family":"Michalak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayanth","family":"Chandran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoon","family":"Shim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mika","family":"Shimoji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Cookson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard L.","family":"Huganir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey D.","family":"Rothstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald L.","family":"Price","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip C.","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee J.","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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