{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T19:45:24Z","timestamp":1788291924135,"version":"build-2803163510"},"reference-count":185,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T00:00:00Z","timestamp":1745452800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Development and Innovation Office, Hungary","award":["2020-1.1.2-PIACI-KFI-2021-00233"],"award-info":[{"award-number":["2020-1.1.2-PIACI-KFI-2021-00233"]}]},{"name":"National Research Development and Innovation Office, Hungary","award":["2024-1.2.2-ERA_NET-2024-00013"],"award-info":[{"award-number":["2024-1.2.2-ERA_NET-2024-00013"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease and other neurodegenerative disorders are characterized by the accumulation of misfolded proteins, such as amyloid-beta, tau, and \u03b1-synuclein, which disrupt neuronal function and contribute to cognitive decline. Heparan sulfate proteoglycans, particularly syndecans, play a pivotal role in the seeding, aggregation, and spreading of toxic protein aggregates through endocytic pathways. Among these, syndecan-3 is particularly critical in regulating the internalization of misfolded proteins, facilitating their propagation in a prion-like manner. This review examines the mechanisms by which syndecans, especially SDC3, contribute to the seeding and spreading of pathological protein aggregates in neurodegenerative diseases. Understanding these endocytic pathways provides valuable insights into the potential of syndecans as biomarkers and therapeutic targets for early intervention in Alzheimer\u2019s disease and other related neurodegenerative disorders.<\/jats:p>","DOI":"10.3390\/ijms26094037","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T11:44:52Z","timestamp":1745495092000},"page":"4037","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Endocytic Pathways Unveil the Role of Syndecans in the Seeding and Spreading of Pathological Protein Aggregates: Insights into Neurodegenerative Disorders"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6294-5345","authenticated-orcid":false,"given":"Anett","family":"Hud\u00e1k","sequence":"first","affiliation":[{"name":"Pharmacoidea Ltd., 6726 Szeged, Hungary"},{"name":"Doctoral School of Theoretical Medicine, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6035-4009","authenticated-orcid":false,"given":"Tam\u00e1s","family":"Letoha","sequence":"additional","affiliation":[{"name":"Pharmacoidea Ltd., 6726 Szeged, Hungary"},{"name":"Doctoral School of Theoretical Medicine, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1002\/ana.24029","article-title":"beta-Amyloid is transmitted via neuronal connections along axonal membranes","volume":"75","author":"Song","year":"2014","journal-title":"Ann. 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