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Metal Chelation as a Potential Therapy for Alzheimer's Disease
Author(s) -
CUAJUNGCO MATH P.,
FAGÉT KYLE Y.,
HUANG XUDONG,
TANZI RUDOLPH E.,
BUSH ASHLEY I.
Publication year - 2000
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2000.tb06938.x
Subject(s) - disease , oxidative stress , neuroscience , neocortex , amyloid beta , alzheimer's disease , acetylcholinesterase , pathogenesis , amyloid (mycology) , medicine , drug development , pharmacology , bioinformatics , chemistry , psychology , drug , pathology , biology , biochemistry , enzyme
A bstract : Alzheimer's disease is a rapidly worsening public health problem. The current lack of effective treatments for Alzheimer's disease makes it imperative to find new pharmacotherapies. At present, the treatment of symptoms includes use of acetyleholinesterase inhibitors, which enhance acetylcholine levels and improve cognitive functioning. Current reports provide evidence that the pathogenesis of Alzheimer's disease is linked to the characteristic neocortical amyloid‐β deposition, which may be mediated by abnormal metal interaction with Aβ as well as metal‐mediated oxidative stress. In light of these observations, we have considered the development of drugs that target abnormal metal accumulation and its adverse consequences, as well as prevention or reversal of amyloid‐β plaque formation. This paper reviews recent observations on the possible etiologic role of Aβ deposition, its redox activity, and its interaction with transition metals that are enriched in the neocortex. We discuss the effects of metal chelators on these processes, list existing drugs with chelating properties, and explore the promise of this approach as a basis for medicinal chemistry in the development of novel Alzheimer's disease therapeutics.