The impact of chelating compounds on Cu2+, Fe2+/3+, and Zn2+ ions in Alzheimer's disease treatment

• Published in: Journal of inorganic biochemistry 2024-08, Vol.257, p.112601, Article 112601
• Main Authors: Mazur, Tomasz, Malik, Magdalena, Bieńko, Dariusz C.
• Format: Article
• Language: English
• Subjects: Acetylcholinesterase inhibitors; Alzheimer's disease; Chelation; Metal complexes; ROS; β-Amyloid
• ISSN: 0162-0134; 1873-3344; 1873-3344
• DOI: 10.1016/j.jinorgbio.2024.112601

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid – β extracellular plaques and tau interfibrillar tangles, leading to memory loss, cognitive decline, and behavioral changes. With dementia posing a growing global health concern, there is an urgent need for comprehensive strategies to address its challenges. The economic burden of dementia is projected to rise significantly, emphasizing the necessity for collaborative efforts in research and healthcare. In the United States alone, millions are affected by AD, with prevalence increasing with age and even affecting younger individuals. The complexity of AD involves intricate biological processes, including the aggregation of amyloid beta, oxidative stress, and metal ion dysregulation. Metal ions, particularly those from copper, iron, and zinc, play pivotal roles in AD pathology, influencing Aβ deposition and tau protein accumulation. Current treatments offer symptomatic relief but do not address the underlying disease mechanisms. This paper explores the potential of various chelating compounds to target metal ions involved in AD pathology. N-acylhydrazones, morpholine, chrysin, quinoline, oxindole, cyclam, catechol-based, and quinazolinone-based derivatives show promising chelation activity and therapeutic effects. Metal chelation therapy offers a targeted approach to AD treatment by addressing the core pathology. By selectively binding to metal ions implicated in disease progression, chelators may minimize side effects associated with broad-spectrum treatments. Additionally, chelators may offer neuroprotective effects beyond metal binding, further enhancing their therapeutic potential. Overall, metal chelation therapy presents a promising strategy in combating AD, with the potential to significantly impact disease progression and improve patient outcomes. [Display omitted] •Description of metal ions pathology, involved in progress of Alzheimer's Disease (AD).•N-acylhydrazones, morpholine, chrysin, quinoline, oxindole, cyclam, catechol and quinazolinone ligands as chelating agents.•The review presents potential therapeutic effects of chelating compounds in Alzheimer's Disease treatment.