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This heterogeneity has limited the effectiveness of the clinically available single\u2010target therapies which only provide symptomatic relief and underscores the need for molecular frameworks capable of addressing multiple pathogenic pathways simultaneously to stop the progression of the disease.<\/jats:p>\n                  <jats:p>Hydrazones have emerged as highly versatile scaffolds in medicinal chemistry thanks to their straightforward synthesis, structural adaptability, and rich repertoire of interaction modes with different biological targets. In recent literature, an increasing number of hydrazone\u2010based molecules have been designed as multitarget\u2010directed ligands (MTDLs) to modulate key enzymes and pathological mechanisms relevant to AD. This review provides a comprehensive and critical overview of hydrazone\u2010containing compounds reported over the last years (2020\u20132025) with potential application in AD therapy, highlighting their activity on classical targets, especially cholinesterases (ChEs), as well as emerging targets including carbonic anhydrase, BACE1, and \u03b1\u2010glycosidase. Particular emphasis is placed on structure\u2013activity relationships (SARs), multitarget profiles, and rational design strategies aimed at exploiting the hydrazone moiety to address the multifactorial nature of AD.<\/jats:p>","DOI":"10.1002\/cmdc.202501097","type":"journal-article","created":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T06:00:00Z","timestamp":1776578400000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exploring the Hydrazone Group in Multifunctional Approaches for Alzheimer's Disease Therapy"],"prefix":"10.1002","volume":"21","author":[{"given":"Carola","family":"Grondona","sequence":"first","affiliation":[{"name":"Department of Pharmacy University of Genoa  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Genoa  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5636-5645","authenticated-orcid":false,"given":"Bruno","family":"Tasso","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Genoa  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,18]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"World Healt Organization Ageing and Health \u201d (2025): Accessed 26 November 2025 Available at:https:\/\/www.who.int\/news\u2010room\/fact\u2010sheets\/detail\/ageing\u2010and\u2010health"},{"key":"e_1_2_9_3_1","unstructured":"M.Prince A.Wimo M.Guerchet G.Ali Y.Wu andM.Prina \u201cWorld Alzheimer Report 2015 The Global Impact of Dementia: An Analysis of Prevalence Incidence Cost and Trends \u201d2015"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy132"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2020.108352"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.4088\/PCC.12r01412"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197-4580(93)90096-T"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70090-5"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308809"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2011.4082"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-021-01569-z"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-023-01851-2"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-024-02087-4"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2022.0315"},{"key":"e_1_2_9_15_1","volume-title":"Grant & Hackh's Chemical Dictionary","author":"Hackh I. 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