{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T22:14:16Z","timestamp":1760220856804,"version":"build-2065373602"},"reference-count":65,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2013,9,17]],"date-time":"2013-09-17T00:00:00Z","timestamp":1379376000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Superoxide dismutase 1 (SOD1) aggregation is one of the pathological markers of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. The underlying molecular grounds of SOD1 pathologic aggregation remains obscure as mutations alone are not exclusively the cause for the formation of protein inclusions. Thus, other components in the cell environment likely play a key role in triggering SOD1 toxic aggregation in ALS. Recently, it was found that ALS patients present a specific altered metabolomic profile in the cerebrospinal fluid (CSF) where SOD1 is also present and potentially interacts with metabolites. Here we have investigated how some of these small molecules affect apoSOD1 structure and aggregation propensity. Our results show that as co-solvents, the tested small molecules do not affect apoSOD1 thermal stability but do influence its tertiary interactions and dynamics, as evidenced by combined biophysical analysis and proteolytic susceptibility. Moreover, these compounds influence apoSOD1 aggregation, decreasing nucleation time and promoting the formation of larger and less soluble aggregates, and in some cases polymeric assemblies apparently composed by spherical species resembling the soluble native protein. We conclude that some components of the ALS metabolome that shape the chemical environment in the CSF may influence apoSOD1 conformers and aggregation.<\/jats:p>","DOI":"10.3390\/ijms140919128","type":"journal-article","created":{"date-parts":[[2013,9,17]],"date-time":"2013-09-17T12:31:17Z","timestamp":1379421077000},"page":"19128-19145","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Small Molecules Present in the Cerebrospinal Fluid Metabolome Influence Superoxide Dismutase 1 Aggregation"],"prefix":"10.3390","volume":"14","author":[{"given":"Joana","family":"Crist\u00f3v\u00e3o","sequence":"first","affiliation":[{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica, Universidade Nova de Lisboa, Av. da Rep\u00fablica, EAN, Oeiras 2784-505, Portugal"}]},{"given":"S\u00f3nia","family":"Leal","sequence":"additional","affiliation":[{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica, Universidade Nova de Lisboa, Av. da Rep\u00fablica, EAN, Oeiras 2784-505, Portugal"}]},{"given":"Isabel","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Molecular Neurobiology Unit, Instituto de Biologia Molecular e Celular, Rua do Campo Alegre, 823, Porto 4150-180, Portugal"},{"name":"Escola Superior de Tecnologia da Sa\u00fade do Porto, Instituto Polit\u00e9cnico do Porto,  Rua Valente Perfeito, 322, Vila Nova de Gaia 4400-330, Portugal"}]},{"given":"Cl\u00e1udio","family":"Gomes","sequence":"additional","affiliation":[{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica, Universidade Nova de Lisboa, Av. da Rep\u00fablica, EAN, Oeiras 2784-505, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2013,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1080\/14660820050515160","article-title":"New consensus research on neuropathological aspects of familial amyotrophic lateral sclerosis with superoxide dismutase 1 (sod1) gene mutations: Inclusions containing sod1 in neurons and astrocytes","volume":"1","author":"Kato","year":"2000","journal-title":"Amyotrophic Lateral Scler. 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