{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T18:20:49Z","timestamp":1791829249152,"version":"4.3.4"},"reference-count":76,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,15]],"date-time":"2025-11-15T00:00:00Z","timestamp":1763164800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Alzheimer\u2019s disease continues to be one of the most urgent neurodegenerative conditions, with acetylcholinesterase (AChE) inhibitors serving as a fundamental component of contemporary treatment approaches. Growing evidence underscores that marine ecosystems are a rich source of structurally varied and biologically active natural products exhibiting anticholinesterase properties. This review presents a thorough synthesis of marine-derived metabolites\u2014including those sourced from bacteria, fungi, sponges, algae, and other marine life\u2014that demonstrate inhibitory effects against AChE and butyrylcholinesterase (BuChE). Numerous compounds, such as meroterpenoids, alkaloids, peptides, and phlorotannins, not only show nanomolar to micromolar inhibitory activity but also reveal additional neuroprotective characteristics, including antioxidant effects, anti-amyloid properties, and modulation of neuronal survival pathways. Despite these encouraging findings, the transition to clinical applications is hindered by a lack of comprehensive pharmacokinetic, toxicity, and long-term efficacy studies. The structural variety of marine metabolites provides valuable frameworks for the development of next-generation cholinesterase inhibitors. Further interdisciplinary research is essential to enhance their therapeutic potential and facilitate their incorporation into strategies for addressing Alzheimer\u2019s disease and related conditions.<\/jats:p>","DOI":"10.3390\/md23110439","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T12:33:04Z","timestamp":1763469184000},"page":"439","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Marine-Derived Natural Substances with Anticholinesterase Activity"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-5018-6696","authenticated-orcid":false,"given":"Daniela","family":"Dimitrova","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy, Medical University of Varna, Tsar Osvoboditel Blv. 84A, 9000 Varna, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5041-1620","authenticated-orcid":false,"given":"Gabriela","family":"Kehayova","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology, and Pharmacotherapy, Medical University of Varna, Tsar Osvoboditel Blv. 84A, 9000 Varna, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6634-5544","authenticated-orcid":false,"given":"Simeonka","family":"Dimitrova","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology, and Pharmacotherapy, Medical University of Varna, Tsar Osvoboditel Blv. 84A, 9000 Varna, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1845-2753","authenticated-orcid":false,"given":"Stela","family":"Dragomanova","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology, and Pharmacotherapy, Medical University of Varna, Tsar Osvoboditel Blv. 84A, 9000 Varna, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Chen, Z.-R., Huang, J.-B., Yang, S.-L., and Hong, F.-F. 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