biostudies-literatureKumar MSNCATS NIH HHSNINDS NIH HHSNIGMS NIH HHS16013https://www.ebi.ac.uk/biostudies/studies/S-EPMC9784173biostudies-literatureUnknown23(24)ALS-linked mutations induce aberrant conformations within the SOD1 protein that are thought to underlie the pathogenic mechanism of SOD1-mediated ALS. Although clinical trials are underway for gene silencing of <i>SOD1</i>, these approaches reduce both wild-type and mutated forms of SOD1. Here, we sought to develop anti-SOD1 nanobodies with selectivity for mutant and misfolded forms of human SOD1 over wild-type SOD1. Characterization of two anti-SOD1 nanobodies revealed that these biologics stabilize mutant SOD1 in vitro. Further, SOD1 expression levels were enhanced and the physiological subcellular localization of mutant SOD1 was restored upon co-expression of anti-SOD1 nanobodies in immortalized cells. In human motor neurons harboring the <i>SOD1 A4V</i> mutation, anti-SOD1 nanobody expInternational journal of molecular sciencesAnti-SOD1 Nanobodies That Stabilize Misfolded SOD1 Proteins Also Promote Neurite Outgrowth in Mutant SOD1 Human Neurons.PMC9784173R01 NS108769R01 GM137529UL1 TR001453R01 NS067206R21 NS120126R01 GM147677R01 NS101895R01 NS118145Kulick DGadd DHDouthwright CYusuf IKumar MSGolebiowski DBosco DAFowler-Magaw MEBoopathy SRotunno MSena-Esteves MBrown RHO'Neil ALXu ZfalseAnti-SOD1 Nanobodies That Stabilize Misfolded SOD1 Proteins Also Promote Neurite Outgrowth in Mutant SOD1 Human Neurons.ALS-linked mutations induce aberrant conformations within the SOD1 protein that are thought to underlie the pathogenic mechanism of SOD1-mediated ALS. Although clinical trials are underway for gene silencing of <i>SOD1</i>, these approaches reduce both wild-type and mutated forms of SOD1. Here, we sought to develop anti-SOD1 nanobodies with selectivity for mutant and misfolded forms of human SOD1 over wild-type SOD1. Characterization of two anti-SOD1 nanobodies revealed that these biologics stabilize mutant SOD1 in vitro. Further, SOD1 expression levels were enhanced and the physiological subcellular localization of mutant SOD1 was restored upon co-expression of anti-SOD1 nanobodies in immortalized cells. In human motor neurons harboring the <i>SOD1 A4V</i> mutation, anti-SOD1 nanobody exp2022-01-01T00:00:00Z2022 Dec2025-04-04T21:55:14.655Z2025-04-04T21:55:14.655ZS-EPMC97841733655565510.3390/ijms232416013