Phenserine improves cognitive performance in rats and is undergoing
phase II clinical trials as an acetylcholinesterase inhibitor.
We found that phenserine imparts a double therapeutic action by targeting 5'UTR sequences in APP mRNA to suppress translation of the precursor, and reduces A(3-peptide secretion with a high degree of specificity. The finding that Df suppresses translational enhancement by 5'UTR sequences in APP mRNA is consistent with evidence for the presence of a modified IRE in the 5'UTR of APP mRNA.
Neither Df or most anticholinesterases is considered to be completely desirable as agents for AD therapy. Desferrioxamine generates hypotension at high doses (Hallaway & Hedlund, 1992), and current anticholinesterases have been shown to be beneficial only for mild cases of AD over 1 year of usage with marked side effects to the liver .
There is clearly a need to develop effective screens to generate more promising APP 5'UTR-directed drugs, such as phenserine, for future clinical us.
We found that phenserine imparts a double therapeutic action by targeting 5'UTR sequences in APP mRNA to suppress translation of the precursor, and reduces A(3-peptide secretion with a high degree of specificity. The finding that Df suppresses translational enhancement by 5'UTR sequences in APP mRNA is consistent with evidence for the presence of a modified IRE in the 5'UTR of APP mRNA.
Neither Df or most anticholinesterases is considered to be completely desirable as agents for AD therapy. Desferrioxamine generates hypotension at high doses (Hallaway & Hedlund, 1992), and current anticholinesterases have been shown to be beneficial only for mild cases of AD over 1 year of usage with marked side effects to the liver .
There is clearly a need to develop effective screens to generate more promising APP 5'UTR-directed drugs, such as phenserine, for future clinical us.
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