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Considering the multifactorial nature of AD, the development of therapies acting on alternative molecular targets is necessary. In this study, we evaluated the neuroprotective effect of a molecule from the hydrozoan Eudendrium carneum and investigated its impact on autophagy-related pathways. Methods: The secretion of E. carneum was fractionated by RP-HPLC according to its neuroprotective activity in SH-SY5Y cells exposed to oA\u03b242, evaluated using LDH and MTT assays. The purified molecule (named EC5), characterized by mass spectrometry, was evaluated regarding in silico toxicity and calcium dynamics. Neuronal lysosomal morphology was assessed using the LysoTracker probe, and cathepsin D activity was determined using a synthetic substrate. The expression of autophagy-related proteins (mTOR, LAMP-1, and LC3B) was evaluated by dot blotting, and amyloid plaque clearance was quantified using Thioflavin-T staining. Results: The steroid glycoside putatively identified as Sarmentoside B (EC5) exhibited neuroprotective effects and showed no toxicity or alterations in neuronal calcium or sodium channel dynamics. EC5 restored lysosomal morphology and cathepsin D activity, reversing the impairment induced by oA\u03b242. Furthermore, EC5 reduced mTOR expression, and this interaction was supported by molecular docking analysis. Lysosomal restoration promoted the clearance of oA\u03b242 aggregates, as evidenced by Thioflavin-T staining, resulting in reduced neuronal death. Conclusions: EC5, putatively identified as Sarmentoside B, exerts neuroprotective effects against oA\u03b242-induced toxicity by promoting autophagy-related amyloid clearance, highlighting its therapeutic potential for AD.<\/jats:p>","DOI":"10.3390\/pharmaceutics18060696","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T03:24:33Z","timestamp":1780629873000},"page":"696","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Putatively Identified Sarmentoside-B Removes Oligomerized Amyloid Peptide from Neurons by Inhibiting mTOR and Restoring Lysosomal Function, in In Vitro Alzheimer\u2019s Disease Model"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-0678-903X","authenticated-orcid":false,"given":"Bruna Rojas","family":"Fr\u00f3es","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Produtos Naturais, Universidade S\u00e3o Francisco, Bragan\u00e7a Paulista 12916-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5159-3959","authenticated-orcid":false,"given":"Juliana Guanaes","family":"Pina","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Produtos Naturais, Universidade S\u00e3o Francisco, Bragan\u00e7a Paulista 12916-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana da Mata","family":"Alves","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Bioqu\u00edmica e Biof\u00edsica, Instituto Butantan, S\u00e3o Paulo 05503-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8423-8213","authenticated-orcid":false,"given":"Alquiandra S. F.","family":"Man\u00e7ano","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Produtos Naturais, Universidade S\u00e3o Francisco, Bragan\u00e7a Paulista 12916-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0068-9974","authenticated-orcid":false,"given":"Fernanda C.","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Centre for Motor Neuron Disease Research, Faculty of Health, Medicine and Behavioural Sciences, Institute for Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7213-206X","authenticated-orcid":false,"given":"Juliana Mozer","family":"Sciani","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Produtos Naturais, Universidade S\u00e3o Francisco, Bragan\u00e7a Paulista 12916-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Haut, F., Argyrousi, E.K., and Arancio, O. 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