期刊
JOURNAL OF NEUROCHEMISTRY
卷 102, 期 4, 页码 1095-1104出版社
WILEY
DOI: 10.1111/j.1471-4159.2007.04613.x
关键词
Alzheimer; curcumin; imaging; multiphoton; neuritic dystrophy; senile plaque
资金
- NIA NIH HHS [AG08487, AG020570, AG024688] Funding Source: Medline
- NIBIB NIH HHS [EB000768] Funding Source: Medline
Alzheimer's disease (AD) is characterized by senile plaques and neuroclegeneration although the neurotoxic mechanisms have not been completely elucidated. It is clear that both oxidative stress and inflammation play an important role in the illness. The compound curcumin, with a broad spectrum of anti-oxidant, anti-inflammatory, and anti-fibrilogenic activities may represent a promising approach for preventing or treating AD. Curcumin is a small fluorescent compound that binds to amyloid deposits. In the present work we used in vivo multi-photon microscopy (MPM) to demonstrate that curcumin crosses the blood-brain barrier and labels senile plaques and cerebrovascular amyloid angiopathy (CAA) in APPswe/ PS1dE9 mice. Moreover, systemic treatment of mice with curcumin for 7 days clears and reduces existing plaques, as monitored with longitudinal imaging, suggesting a potent disaggregation effect. Curcumin also led to a limited, but significant reversal of structural changes in dystrophic dendrites, including abnormal curvature and dystrophy size. Together, these data suggest that curcurnin reverses existing amyloid pathology and associated neurotoxicity in a mouse model of AD. This approach could lead to more effective clinical therapies for the prevention of oxidative stress, inflammation and neurotoxicity associated with AD.
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