| Autor: |
Leiteritz, Anne, Dilberger, Benjamin, Wenzel, Uwe, Fitzenberger, Elena, Justus Liebig University Giessen |
| Rok vydání: |
2018 |
| Předmět: |
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| DOI: |
10.22029/jlupub-8820 |
| Popis: |
Background: The neurodegenerative disorder Alzheimer´s disease is caused by the accumulation of toxic aggregates of betha-amyloid in the human brain. On the one hand, hyperhomocysteinemia has been shown to be a risk factor for cognitive decline in Alzheimer´s disease. On the other hand, betaine has been demonstrated to attenuate Alzheimer-like pathological changes induced by homocysteine. It is reasonable to conclude that this is due to triggering the remethylation pathway mediated by betaine-homocysteine-methyltransferase. In the present study, we used the transgenic Caenorhabditis elegans strain CL2006, to test whether betaine is able to reduce betha-amyloid-induced paralysis in C. elegans. This model expresses human betha-amyloid 1-42 under control of a muscle-specific promoter that leads to progressive, age-dependent paralysis in the nematodes. Results: Betaine at a concentration of 100 μM was able to reduce homocysteine levels in the presence and absence of 1 mM homocysteine. Simultaneously, betaine both reduced normal paralysis rates in the absence of homocysteine and increased paralysis rates triggered by addition of homocysteine. Knockdown of cystathionine-betha-synthase using RNA interference both increased homocysteine levels and paralysis. Additionally, it prevented the reducing effects of betaine on homocysteine levels and paralysis. Conclusion: Our studies show that betaine is able to reduce homocysteine levels and betha-amyloid-induced toxicity in a C. elegans model for Alzheimer´s disease. This effect is independent of the remethylation pathway but requires the transsulfuration pathway mediated by cystathionine-betha-synthase. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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