title: Evaluating the Effectiveness of GTM-1, Rapamycin, and Carbamazepine on Autophagy and Alzheimer Disease.
abstract: BACKGROUND This study was proposed to compare the efficacy and safety of GTM-1, Rapamycin (Rap), and Carbamazepine (CBZ) in managing Alzheimer disease (AD). The impact of the above mentioned therapeutic drugs on autophagy was also investigated in our study. MATERIAL AND METHODS Firstly, 3×Tg AD mice were randomly allocated into 4 groups (each group with 10 mice), in which AD mice were separately treated with dimethylsulfoxide (DMSO, vehicle group), GTM-1 (6 mg/kg), Rap (1 mg/kg), and CBZ (100 mg/kg). Then spatial memory and learning ability of mice was tested using the Morris water maze. Routine blood tests were performed to evaluate the toxicity of these drugs. Amyloid-β42 (Aβ42) concentration was detected by ELISA and immunohistochemistry. Proteins related to autophagy were detected by Western blot. RESULTS GTM-1, Rap, and CBZ significantly improved the spatial memory of 3×Tg AD mice compared to that in the vehicle group (all P<0.05). Moreover, this study revealed that CBZ dosage was related to toxicity in mice. All of the above drugs significantly increased the expression of LC3-II and reduced Aβ42 levels in hippocampi of 3×Tg AD mice (all P<0.05). On the other hand, neither GTM-1 nor CBZ had significant influence on the expression of proteins on the mTOR pathway. CONCLUSIONS GTM-1 can alleviate the AD syndrome by activating autophagy in a manner that is dependent on the mTOR pathway and it therefore can be considered as an alternative to Rap.
authors.affiliation: Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai, China (mainland).
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai, China (mainland).
authors.forename: Lina
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, 85 Hospital of People's Liberation Army, Shanghai, China (mainland).
authors.forename: Run
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai, China (mainland).
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai, China (mainland).
authors.forename: Haoyue
authors.initials: H
authors.lastname: Che
authors.affiliation: Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai, China (mainland).
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai, China (mainland).
authors.forename: Peng
authors.initials: P
authors.lastname: Fu
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D002220:Carbamazepine / Q000494:pharmacology*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D058225:Plaque, Amyloid / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011799:Quinazolines / Q000494:pharmacology*; D011897:Random Allocation; D020123:Sirolimus / Q000494:pharmacology*; D065852:Spatial Memory / Q000187:drug effects
chemical_list: C000589446:GTM-1 compound; D018696:Neuroprotective Agents; D011799:Quinazolines; D002220:Carbamazepine; D020123:Sirolimus