ABSTRACT
AIM: To clarify if TA9901, a natural antioxidants, could inhibit the formation of ?-amyloid(A?) fibril when A? 1-40 were injected into cerebral cortex of rat brain, and explore the mechanism of action of TA9901 on Alzheimer disesse. METHODS: Twelve Wistar rats (250-300 g) were randomly divided into four groups ( n=3 ). (1) control group; (2) TA9901 treatment group (ip. 100 mg?kg -1 ?d -1 ); (3) Vitamin E(VE) treatment group (ip. 100 mg?kg -1 ?d -1 ); (4) PBS group. 5 ?L 0.2% A? 1-40 was immediately injected into the right side of the deep cerebral cortex of control, TA9901 and VE group rats. The animals were sacrificed at the seventh day after the injection. The sections of the rat brain that contained the injected field were examined with transmission electron microscopy and Congo red staining with polarized microscopy. RESULTS: Many depositions of high electron density were observed by electron microscopy in the field where A? 1-40 was injected. They are intimately intermingled with macrophages and astrocytes. In the field, about 10nm fibrillar structures were observed that appeared similar to the fibrils seen in senile plaque (SP) of the brain of Alzheimer disease (AD). The fields in control and VE group contained richer A? fibrils than that in TA9901 group. After the sections stained with Congo red, A? 1-40 aggregation demonstrated intense birefringence under, indication the formation of amyloid fibrils. In TA9901 group, there was a weak birefringence.CONCLUSIONS: TA9901 can inhibit the fibril formation of A? that was injected into deep cerebral cortex of rat brain, this indicates primarily that TA9901 may be a potential therapeutic drug to interfere with the progression of amyloidgenesis in AD.
ABSTRACT
AIM: To investigate the mechanism that antioxidants TA9901, inhibit the formation of amyloid-?-protein(A?) fibril. METHODS: Fourier-transform infrared spectroscopy was used to study the secondary structure changes on aging A? in vitro. RESULTS: A? aged alone for 30 min, the content of ?-pleated sheet and ?-turn were 43.17% and 32.9% respectively. A? aged alone for 7 days, the content of ?-pleated sheet increased abuot 10% and produced a shift of random coil toward ?-pleated sheet. TA9901 induced a significant decrease of the content of ?-turn (23.5%) and ?-pleated sheet (26.4%). VE mainly decreased the ?-pleated sheet content (30.8%). The combination of TA9901 and VE promoted transition of ?-turn (16.7%) toward ?-helix and random coil. CONCLUSIONS: Both of TA9901 and VE can effectively diminish the ?-structural content. TA9901 showed more intensitive inhibition than VE. The effect of TA9901 on the secondary structure of aged A? was associated with the mechanism that TA9901 inhibited A? aggregation and fibril formation.