The Experimental Alzheimer's Disease Drug Posiphen [(+)-Phenserine] Lowers Amyloid-β Peptide Levels in Cell Culture and Mice
| العنوان: | The Experimental Alzheimer's Disease Drug Posiphen [(+)-Phenserine] Lowers Amyloid-β Peptide Levels in Cell Culture and Mice |
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| المؤلفون: | De Mao Chen, Nigel H. Greig, Kumar Sambamurti, Harold W. Holloway, Tada Utsuki, Qian Sheng Yu, Debomoy K. Lahiri, Bryan Maloney, Tony Giordano |
| المصدر: | Journal of Pharmacology and Experimental Therapeutics. 320:386-396 |
| بيانات النشر: | American Society for Pharmacology & Experimental Therapeutics (ASPET), 2006. |
| سنة النشر: | 2006 |
| مصطلحات موضوعية: | Male, Amyloid, medicine.drug_class, Physostigmine, Alpha (ethology), Pharmacology, Amyloid beta-Protein Precursor, Mice, Alzheimer Disease, In vivo, Cell Line, Tumor, mental disorders, medicine, Animals, Humans, RNA, Messenger, Senile plaques, Cerebral Cortex, Amyloid beta-Peptides, Dose-Response Relationship, Drug, Chemistry, Stereoisomerism, Mice, Inbred C57BL, Dose–response relationship, Acetylcholinesterase inhibitor, Biochemistry, Cell culture, Molecular Medicine, Cholinergic, Cholinesterase Inhibitors, Amyloid Precursor Protein Secretases |
| الوصف: | Major characteristics of Alzheimer's disease (AD) are synaptic loss, cholinergic dysfunction, and abnormal protein depositions in the brain. The amyloid beta-peptide (Abeta), a proteolytic fragment of amyloid beta precursor protein (APP), aggregates to form neuritic plaques and has a causative role in AD. A present focus of AD research is to develop safe Abeta-lowering drugs. A selective acetylcholinesterase inhibitor, phenserine, in current human trials lowers both APP and Abeta. Phenserine is dose-limited in animals by its cholinergic actions; its cholinergically inactive enantiomer, posiphen (+)-[phenserine], was assessed. In cultured human neuroblastoma cells, posiphen, like phenserine, dose- and time-dependently lowered APP and Abeta levels by reducing the APP synthesis rate. This action translated to an in vivo system. Posiphen administration to mice (7.5-75 mg/kg daily, 21 consecutive days) significantly decreased levels of total APP (tissue mass-adjusted) in a dose-dependent manner. Abeta40 and Abeta42 levels were significantly lowered by posiphen (> or =15 mg/kg) compared with controls. The activities of alpha-, beta-, and gamma-secretases were assessed in the same brain samples, and beta-secretase activity was significantly reduced. Posiphen, like phenserine, can lower Abeta via multiple mechanisms and represents an interesting drug candidate for AD treatment. |
| تدمد: | 1521-0103 0022-3565 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6439ed5b30d25eb61d50559b7b7ec3dcTest https://doi.org/10.1124/jpet.106.112102Test |
| رقم الانضمام: | edsair.doi.dedup.....6439ed5b30d25eb61d50559b7b7ec3dc |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15210103 00223565 |
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