Journal
ACS CHEMICAL NEUROSCIENCE
Volume 3, Issue 11, Pages 919-927Publisher
AMER CHEMICAL SOC
DOI: 10.1021/cn300060v
Keywords
Amyloid; Alzheimer's disease; aggregates; copper; zinc; chelate
Funding
- TCU start-up funds
- TCU Research and Creative Activities Fund
- Robert A. Welch Foundation [P-1760]
- NIH [P01 AG022550, P01 AGAG027956, T32 AG020494]
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Alzheimer's disease is. a neurodegenerative disorder characterized by the development of intracellular neurofibrillary tangles, deposition of extracellular amyloid beta (A beta) plaques, along with a disruption of transition metal ion homeostasis in conjunction with oxidative stress. Spectroscopic, transmission electron microscopy, and scanning electron microscopy imaging studies show that 1 (pyclen) is capable of both preventing and disrupting Cu2+ induced AB(1-40) aggregation. The pyridine backbone of 1 engenders antioxidant capacity, as shown by cellular DCFH-DA (dichlorodihydrofluorescein diacetate) assay in comparison to other N-heterocyclic amines lacking this aromatic feature. Finally, 1 prevents cell death induced by oxidative stress as shown by the Calcein AM assay. The results are supported using density functional theory studies which show that the pyridine backbone is responsible for the antioxidant capacity observed.
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