{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T07:40:33Z","timestamp":1767339633687,"version":"3.43.0"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T00:00:00Z","timestamp":1754611200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a complex neurodegenerative disorder characterized by the intracellular deposition of Tau protein and extracellular deposition of amyloid-\u03b2 peptide (A\u03b2). AD is also characterized by neuroinflammation and synapse loss, among others. The S100 family is a group of calcium-binding proteins with intra- and extracellular functions, that are important modulators of inflammatory responses. S100B, which is upregulated in AD patients and the most abundant member of this family, was shown to inhibit <jats:italic>in vitro<\/jats:italic> the aggregation and toxicity of A\u03b242, acting as a neuroprotective holdase-type chaperone. Although S100B is primarily produced by astrocytes, it is also expressed by various cells, including neurons. In this work, we investigated if S100B neuronal expression is triggered as a response to A\u03b2 toxic species, to provide protection during disease progression. We used the AD mouse model A\u03b2PPswe\/PS1A246E to show that neuronal S100B levels are significantly higher in 10-month-old animals, and cellular assays to demonstrate that A\u03b2 oligomers significantly increase S100B expression in SH-SY5Y cells, but not monomeric or fibrillar A\u03b2. Using primary cultures of rat hippocampal neurons, we showed that S100B partially reverts A\u03b2-induced cofilin-actin rods (synapse disruptors), and rescues the decrease in active synapses and post-synaptic marker (PSD-95), imposed by A\u03b2 peptide. Altogether, these findings establish the neuroprotective activity of S100B in response to proteotoxic stress in cells, highlighting its chaperone function as a crucial factor in understanding proteostasis regulation in the diseased brain and identifying potential therapeutic targets.<\/jats:p>","DOI":"10.3389\/fnmol.2025.1636365","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T05:27:34Z","timestamp":1754630854000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Neuronal expression of S100B triggered by oligomeric A\u03b2 peptide contributes to protection against cytoskeletal damage and synaptic loss"],"prefix":"10.3389","volume":"18","author":[{"given":"Joana","family":"Saavedra","sequence":"first","affiliation":[]},{"given":"Mariana","family":"Nascimento","sequence":"additional","affiliation":[]},{"given":"Ant\u00f3nio J.","family":"Figueira","sequence":"additional","affiliation":[]},{"given":"Marina I.","family":"Oliveira da Silva","sequence":"additional","affiliation":[]},{"given":"Tiago","family":"Gi\u00e3o","sequence":"additional","affiliation":[]},{"given":"Jo\u00e3o","family":"Oliveira","sequence":"additional","affiliation":[]},{"given":"M\u00e1rcia A.","family":"Liz","sequence":"additional","affiliation":[]},{"given":"Cl\u00e1udio M.","family":"Gomes","sequence":"additional","affiliation":[]},{"given":"Isabel","family":"Cardoso","sequence":"additional","affiliation":[]}],"member":"1965","published-online":{"date-parts":[[2025,8,8]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2726","DOI":"10.3390\/cells10102726","article-title":"Cofilin and actin dynamics: multiple modes of regulation and their impacts in neuronal development and degeneration","volume":"10","author":"Bamburg","year":"2021","journal-title":"Cells"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1038\/nn.3028","article-title":"The toxic a\u03b2 oligomer and Alzheimer\u2019s disease: an emperor in need of clothes","volume":"15","author":"Benilova","year":"2012","journal-title":"Nat. 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