Treatment with Fleeceflower Derivative Blocks Plaque Formation in Mouse Alzheimer's Disease Model

In previous studies, these mice demonstrated cognitive impairments beginning at four months of age and developed amyloid plaques in the brain that were evident by 10 months.

In the current study Tg mice were treated with varying doses of tetrahydroxystilbene glucoside (TSG), the active compound derived from the Chinese herbal medicine tuber fleeceflower (Polygonum multiflorum Thunb). The drug was given to 4- or 10- month-old animals for a period of six months. At the end of the treatment, cDNA microarray analysis, reverse transcription PCR, western blotting, and immunochemical techniques were used to determine levels of alpha-synuclein messenger RNA (mRNA) and protein expression. Accumulation of alpha-synuclein leads to the formation of insoluble aggregates that have been implicated in several neurodegenerative diseases, including Parkinson's disease, dementia with Lewy bodies, and Alzheimer's disease.

Results published in the January 2013 issue of the journal Restorative Neurology and Neuroscience revealed that alpha-synuclein mRNA expression increased in the hippocampus of four-month to 16-month old Tg mice compared with age-matched non-Tg controls. Alpha-synuclein protein expression in the hippocampus also increased significantly in four-month to 16-month old Tg mice. Significant down-regulation of alpha-synuclein mRNA and protein expression in the hippocampus was found after treatment with TSG for six months in both 10- and 16-month-old Tg mice. Production of dimers and tetramers of alpha-synuclein protein in Tg mice was inhibited after treatment with TSG.

The expression and aggregation of alpha-synuclein increased in an age-dependent fashion in Tg mice. TSG not only prevented over-expression of alpha-synuclein at an early stage, but also reversed the increased expression of alpha-synuclein and inhibited aggregation at the late stage of Tg mice. Therefore, TSG may have potential to prevent and treat Alzheimer's disease.

"Our results raise the possibility that TSG might be a novel compound for the treatment of Alzheimer's disease and dementia with Lewy body," said first author Dr. Lan Zhang, associate professor of pharmacology at Capital Medical University. "The role of alpha-synuclein, especially in the early phase of Alzheimer's disease, and its interaction with amyloid-beta should be considered when developing new therapeutic strategies to target Alzheimer's disease."

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