{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T04:04:33Z","timestamp":1792037073667,"version":"4.4.0"},"reference-count":241,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T00:00:00Z","timestamp":1677456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The concept of chelation therapy as a valuable therapeutic approach in neurological disorders led us to develop multi-target, non-toxic, lipophilic, brain-permeable compounds with iron chelation and anti-apoptotic properties for neurodegenerative diseases, such as Parkinson\u2019s disease (PD), Alzheimer\u2019s disease (AD), age-related dementia and amyotrophic lateral sclerosis (ALS). Herein, we reviewed our two most effective such compounds, M30 and HLA20, based on a multimodal drug design paradigm. The compounds have been tested for their mechanisms of action using animal and cellular models such as APP\/PS1 AD transgenic (Tg) mice, G93A-SOD1 mutant ALS Tg mice, C57BL\/6 mice, Neuroblastoma \u00d7 Spinal Cord-34 (NSC-34) hybrid cells, a battery of behavior tests, and various immunohistochemical and biochemical techniques. These novel iron chelators exhibit neuroprotective activities by attenuating relevant neurodegenerative pathology, promoting positive behavior changes, and up-regulating neuroprotective signaling pathways. Taken together, these results suggest that our multifunctional iron-chelating compounds can upregulate several neuroprotective-adaptive mechanisms and pro-survival signaling pathways in the brain and might function as ideal drugs for neurodegenerative disorders, such as PD, AD, ALS, and aging-related cognitive decline, in which oxidative stress and iron-mediated toxicity and dysregulation of iron homeostasis have been implicated.<\/jats:p>","DOI":"10.3390\/cells12050763","type":"journal-article","created":{"date-parts":[[2023,2,28]],"date-time":"2023-02-28T03:29:46Z","timestamp":1677554986000},"page":"763","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["The Neuroprotective Activities of the Novel Multi-Target Iron-Chelators in Models of Alzheimer\u2019s Disease, Amyotrophic Lateral Sclerosis and Aging"],"prefix":"10.3390","volume":"12","author":[{"given":"Lana","family":"Kupershmidt","sequence":"first","affiliation":[{"name":"Clinical Research Institute at Rambam Health Care, Haifa 31096, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moussa B. H.","family":"Youdim","sequence":"additional","affiliation":[{"name":"Technion-Rappaport Family Faculty of Medicine, Haifa 31096, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1007\/s11357-022-00591-7","article-title":"From 1901 to 2022, how far are we from truly understanding the pathogenesis of age-related dementia?","volume":"44","author":"Fang","year":"2022","journal-title":"Geroscience"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/0163-7258(94)90055-8","article-title":"Oxidative stress: Free radical production in neural degeneration","volume":"63","author":"Gotz","year":"1994","journal-title":"Pharmacol. 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