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The Role of Natural Products in the Discovery of New Drug Candidates for the Treatment of Neurodegenerative Disorders II: Alzheimer's Disease

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The present review is part II in a series (part I focuses on Parkinson's Disease) that addresses the value of natural product chemistry in the discovery of medicines for the treatment of neurodegenerative disorders. Data reviewed document that a host of products from plant species and derivatives have neuroprotectant effects in vitro and in vivo. In addition, besides neuroprotection, natural products also demonstrate biological effects that target biochemical pathways underlying associated symptoms of neurdegnerative disorders that include cognitive impairments, energy/fatigue, mood, and anxiety. This part of the review series focuses specifically upon Alzheimer's Disease (AD). AD is postulated to result from extracellular formation of amyloid plaques and intracellular deposits of neurofibrilary tangles in the hippocampus, cerebral cortex and other areas of the brain essential for cognitive function. Plaques are formed mostly from the deposition β-amyloid (Aβ), a peptide derived from the amyloid precursor protein (APP). Filamentous tangles are formed from paired helical filaments composed of neurofilament and hyperphosphorilated tau protein, a microtubule-associated protein. In addition, environmental factors can engender the production of cytokines that are closely related to the installation of an inflammatory process that contributes to neuronal death and the development and the progression of AD. In this review we focus on the recent main contribuitions of natural products chemistry to the discovery of new chemical entities usefull to the control and prevention of AD installation and progression. More than sixteen plant species, including Ginseng, Celastrus paniculatus, Centella asiatica, Curcuma longa, Ginkgo biloba, Huperzia serrata, Lycoris radiate, Galanthus nivalis, Magnolia officinalis, Polygala tenuifolia, Salvia lavandulaefolia, Salvia miltiorrhiza, Coptis chinensis, Crocus sativus, Evodia rutaecarpa, Sanguisorba officinalis, Veratrum grandiflorum and Picrorhiza kurvoa, are discussed as potential sources of active extracts. In addition, more than sixty secondary metabolites are under evaluation for their efficacy on controlling symptoms and to impede the development and progression of AD.

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Keywords: Alzheimer's disease; Neurodegenerative disorders; Parkinson's disease; biodiversity; drug discovery; medicinal chemistry; natural products

Document Type: Research Article

Publication date: March 1, 2011

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  • CNS & Neurological Disorders - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in neurological and central nervous system (CNS) disorders e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will contain a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in neurological and CNS disorders. As the discovery, identification, characterization and validation of novel human drug targets for neurological and CNS drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.
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