Objectives : Many neurcdegenerative disorders and syndmmes are assodated with an excessive generation of reactive oxygen species (ROS) and oxidative stress. The pathways to nerve cell death induced by diverse potential neurotoxins such as peptides, excitatory amino acids commonly share oxidative downstseam processes, which can cause either an acute oxidative destruction or activate secondary events leading to apoptosis. Thus, A beta may not be the sole active fragment of beta-amyloid precursor protein (betaAPP) in the neurotoxicity associated with Alzheimer´diseaAAD). The pathophysiological role of CT105 derived APp695 has been intensively studied with CT105 expressing cell lines in vitro models of chronic neurodegenerative diseases such as AD.
Methods : We focused on the amyloidegenic carboxyl terminal fragments of betaAPP containing the full length of A beta (CT105). We constructed a pCT105(carboxy-tenninal 105 amino acid fragment) of beta APP, examined the effects of CT105 in neuroblastoma cell lines. We established Ramulus et Uncus Uncariae water extract(RAM) against the CT105 and used them for the Western blot, RT-FCR. Tunel assay and immunccytochemishy analysis. Findings from our experiments have shown that RAM water extract may play an important role in protection and suppression against apoptosis induced by APP metabolic fragments (beta-amyloid [Abetal. carboxyl terminal [CT1051). which bas neumprotective activities in concentration-dependent (>15 micromoVd) and prevented CT(lG5-induced cytotoxicity in cultured neumblastoma cell lines. Also. RAM inhibited CT(105)binduced cytotoxicity when SK-N-SH cells was transfected with CT105. We have shown that RAM water extract inhibited and protect4 apoptotic effect by CT105, was shown to induce expression of cdc42, p38 MAF´K and extncellular signal-regulated kinases(ERK). in conbast expression of Caspase 3. iNOS and calpain by CT105 was suppressed when CT105 expression were incubated with RAM treabnent, which was confiied by RT-FCR and Western blot analysis. These results indicate that have also provided a molecular basis for the potential of using specific inhibitors for treating Alzheimer´s disease (AD).
Results : From these results, we proposed that RAM treabnent might improve the not only by suppressing apoptotic induction, but also by protecting CT(l05Finduced eurotoxicity probably through the increased expression of CT105 in neuroblastoma cells
Conclusion : These observations suggest that RAM water extract may be alternative substances for the treatment of AD and may provide a potentially useful therapeutic strategy for advanced Alzheimer´s disease(AD).
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