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Diet plant components with multitarget functions are promising compounds in the prevention of AD and PD. Our aim was to identify neuroprotective compounds from Annurca apple polyphenol extract (AFPE). Methods: AFPE was fractionated by gel filtration, and the eluted peaks were subjected to chemical analyses (i.e., RP-HPLC and mass spectrometry), determination of inhibitory enzyme activity and cell effects by MTT, and morphology assays. Results: In AFPE, we identified thaumatin-like protein 1a, belonging to the pathogenesis-related protein (PR) family. This protein showed the best inhibitory activity on AChE, MAO-A (IC50 = 5.53 \u00b5M and 1.71 \u00b5M, respectively), and A\u03b21\u201340 fibril aggregation (IC50 = 9.16 \u00b5M), compared to AFPE and other polyphenol-containing fractions. Among the latter, Peak 4 reverted A\u03b2 fibril formation (IC50 = 104.87 \u00b5M). Moreover, thaumatin-like protein 1a protected AGS and MKN-28 cells from serum-deprivation-induced stress conditions. Conclusions: We showed that AFPE exerted neuroprotective functions not only through its polyphenols but also through thaumatin-like protein 1a, which acted like a multitarget molecule.<\/jats:p>","DOI":"10.3390\/nu16020307","type":"journal-article","created":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T08:58:13Z","timestamp":1705654693000},"page":"307","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Identification and Characterization of Neuroprotective Properties of Thaumatin-like Protein 1a from Annurca Apple Flesh Polyphenol Extract"],"prefix":"10.3390","volume":"16","author":[{"given":"Antonio","family":"D\u2019Errico","sequence":"first","affiliation":[{"name":"Department of Medical, Movement and Well-Being Sciences (DiSMMeB), University of Naples \u201cParthenope\u201d, Via Medina 40, 80133 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosarita","family":"Nasso","sequence":"additional","affiliation":[{"name":"Department of Medical, Movement and Well-Being Sciences (DiSMMeB), University of Naples \u201cParthenope\u201d, Via Medina 40, 80133 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9595-9665","authenticated-orcid":false,"given":"Antimo","family":"Di Maro","sequence":"additional","affiliation":[{"name":"Department of Environmental, Biological and Pharmaceutical Sciences and Technologies (DiSTABiF), University of Campania \u201cLuigi Vanvitelli\u201d, Via Vivaldi 43, 81100 Caserta, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Landi","sequence":"additional","affiliation":[{"name":"Department of Environmental, Biological and Pharmaceutical Sciences and Technologies (DiSTABiF), University of Campania \u201cLuigi Vanvitelli\u201d, Via Vivaldi 43, 81100 Caserta, Italy"},{"name":"Institute of Crystallography, National Research Council of Italy, Via Vivaldi 43, 81100 Caserta, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5136-0941","authenticated-orcid":false,"given":"Angela","family":"Chambery","sequence":"additional","affiliation":[{"name":"Department of Environmental, Biological and Pharmaceutical Sciences and Technologies (DiSTABiF), University of Campania \u201cLuigi Vanvitelli\u201d, Via Vivaldi 43, 81100 Caserta, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2235-6302","authenticated-orcid":false,"given":"Rosita","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Environmental, Biological and Pharmaceutical Sciences and Technologies (DiSTABiF), University of Campania \u201cLuigi Vanvitelli\u201d, Via Vivaldi 43, 81100 Caserta, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7585-5052","authenticated-orcid":false,"given":"Stefania","family":"D\u2019Angelo","sequence":"additional","affiliation":[{"name":"Department of Medical, Movement and Well-Being Sciences (DiSMMeB), University of Naples \u201cParthenope\u201d, Via Medina 40, 80133 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4485-7383","authenticated-orcid":false,"given":"Mariorosario","family":"Masullo","sequence":"additional","affiliation":[{"name":"Department of Medical, Movement and Well-Being Sciences (DiSMMeB), University of Naples \u201cParthenope\u201d, Via Medina 40, 80133 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosaria","family":"Arcone","sequence":"additional","affiliation":[{"name":"Department of Medical, Movement and Well-Being Sciences (DiSMMeB), University of Naples \u201cParthenope\u201d, Via Medina 40, 80133 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"572090","DOI":"10.3389\/fnagi.2020.572090","article-title":"Aging and Neurodegenerative Disease: Is the Adaptive Immune System a Friend or Foe?","volume":"12","author":"Mayne","year":"2020","journal-title":"Front. 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