Marine natural products as aβ modulators

被引：0
|
作者：
Garcia-Palomero, E. [1 ]
Usan, P. [1 ]
Garcia, P. [1 ]
Delgado, E. [1 ]
de Austria, C. [1 ]
Saiz, G. [1 ]
Perez, M. A. [1 ]
Sanchez-Quesada, J. [1 ]
Dorronsoro, I [1 ]
Castro, A. [1 ]
Medina, M. [1 ]
机构：
[1] Noscira SA, Tres Cantos, Madrid, Spain
来源：
NEW TRENDS IN ALZHEIMER AND PARKINSON RELATED DISORDERS: ADPD 2009 | 2009年
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中图分类号：
R74 [神经病学与精神病学];
学科分类号：
摘要：
We have developed a drug discovery program in order to look for neuroprotective compounds from marine origin, showing biological activities relevant for preventing and/or treating neurodegenerative diseases. Thus, we have identified a family of marine compounds showing potent neuroprotective activity in several cellular models of oxidative stress. These molecules are also able to significantly reduce beta-amyloid (A beta) secretion in APP-transfected cell lines. This effect correlates with an increase of soluble APP (sAPP) and alpha APP (alpha APP) fragments, indicating that activation of the a-secretase pathway is involved. Additional experiments seem to suggest that these compounds could activate metalloproteases which are implicated in the A beta degradation. An active medicinal chemistry program has been developed, leading to several naturally-derived synthetic lead compounds with improved potency and ADME properties.
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页码：135 / 139
页数：5
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