{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T03:14:07Z","timestamp":1777605247316,"version":"3.51.4"},"reference-count":86,"publisher":"Society for Neuroscience","issue":"11","license":[{"start":{"date-parts":[[2004,9,17]],"date-time":"2004-09-17T00:00:00Z","timestamp":1095379200000},"content-version":"vor","delay-in-days":184,"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":[[2004,3,17]]},"abstract":"<jats:p>The pathogenesis of neurodegenerative diseases is believed to involve abnormal aggregation of proteins, but the mechanisms initiating protein aggregation are unclear. Here we report a novel phenomenon that could be instrumental in triggering protein aggregation in neurodegenerative diseases. We show that the 3\u2032 untranslated region (3\u2032UTR) of a light neurofilament (NF-L) transcript enhances the reactivity of its own translated product and leads to loss of solubility and aggregation of NF-L protein and to coaggregation of mutant superoxide dismutase 1 (SOD1) protein. Full-length mouse NF-L cDNAs, with and without NF-L 3\u2032UTR, were fused to the C terminus of a green fluorescent protein (GFP) reporter gene, and the GFP-tagged NF-L proteins were examined in transfected Neuro2a cells. The GFP-tagged NF-L protein expressed from the transgene containing NF-L 3\u2032UTR, but not from the transgene lacking NF-L 3\u2032UTR, colocalizes with endogenous heavy neurofilament protein and, at high-level expression, leads to loss of solubility and aggregation of GFP-tagged NF-L protein. Aggregation of GFP-tagged NF-L protein triggers coaggregation and loss of solubility of coexpressed DsRed-tagged mutant (G93A) SOD1 protein but not wild-type SOD1 protein. Deletional mutagenesis maps the RNA sequence causing aggregation of GFP-tagged NF-L protein to the proximal 45 nucleotides of NF-L 3\u2032UTR. This is the site of a major destabilizing element in NF-L RNA and binding site for RNA-binding proteins. Our findings support a working model whereby NF-L RNA, or cognate RNA-binding factors, enhances the reactivity of NF-L protein and provides a triggering mechanism leading to aggregation of NF-L and other proteins in neurodegenerative diseases.<\/jats:p>","DOI":"10.1523\/jneurosci.5689-03.2004","type":"journal-article","created":{"date-parts":[[2004,3,17]],"date-time":"2004-03-17T20:57:53Z","timestamp":1079557073000},"page":"2716-2726","source":"Crossref","is-referenced-by-count":27,"title":["3\u2032 Untranslated Region in a Light Neurofilament (NF-L) mRNA Triggers Aggregation of NF-L and Mutant Superoxide Dismutase 1 Proteins in Neuronal 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