Contribution by Chinese Authors in BSP Journal: Current Alzheimer Research

1. Pan-Amyloid Oligomer Specific scFv Antibody Attenuates Memory Deficits and Brain Amyloid Burden in Mice with Alzheimer’s Disease

Author(s): Min Zhao, Shao-wei Wang, Yu-jiong Wang, Ran Zhang, Ya-nan Li, Ya-jing Su, Wei-wei Zhou, Xiao-lin Yu and Rui-tian Liu

Affiliation: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.

Abstract

Amyloid oligomers have a critical function in the pathologic processes of various amyloidoses, such as Alzheimer’s disease (AD), Parkinson disease (PD), Huntington’s disease, prion-related diseases, type 2 diabetes, and hereditary renal amyloidosis. Our previous reports demonstrated that a conformation-dependent oligomer-specific single-chain variable fragment (scFv) antibody, W20, isolated from a naïve human scFv library, can recognize oligomers assembled from α -synuclein, amylin, insulin, A β40/42, prion peptide 106–126, and lysozyme, inhibit the aggregation of various amyloid, and attenuate amyloid oligomer-induced cytotoxicity In vitro. Furthermore, W20 recognized the amyloid oligomers in all types of plaques, Lewy bodies, and amylin deposits in the brain tissues of AD and PD patients and in the pancreas of type 2 diabetes patients. In the current study, we showed that W20 blocked the binding of Aβ oligomers to SH-SY5Y cells, did not bind to heat shock protein, rescued cognitive impairments in APP/PS1 transgenic mice, and interfered with Aβ levels and deposits in mouse brain. These results suggest that W20 may be a promising therapeutic for the treatment of AD.

 

2. Autophagy Enhancer Carbamazepine Alleviates Memory Deficits and Cerebral Amyloid-β Pathology in a Mouse Model of Alzheimer’s Disease

Author(s): Lixi Li, Sufang Zhang, Xin Zhang, Ting Li, Yu Tang, Hui Liu, Wendi Yang and Weidong Le

Affiliation: Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.

Abstract

Autophagy plays an important role in Alzheimer’s disease (AD). It has been reported that autophagic flux is altered in patients with AD, and application of the autophagy enhancer rapamycin may alleviate the cognitive impairment and amyloid-β (Aβ) neuropathology in transgenic animal model of AD. Since rapamycin is also an immune suppressor, there is a concern that long-term use of rapamycin may bring severe unwanted side effects. The aim of this study is to test if carbamazepine (CBZ), an anti-epileptic drug that has a potent autophagy enhancement effect, has anti-AD effects in APPswe/PS1deltaE9 transgenic mice model of AD. We found that APPswe/PS1deltaE9 mice display increased autophagic activity accompanied by decreased mTOR activity. After three months treatment with CBZ in the APPswe/PS1deltaE9 mice, we demonstrated that the spatial learning and memory deficits in these mice are significantly alleviated. We also documented that the cerebral amyloid plaque burden and Aβ42 levels in these mice are significantly reduced. Furthermore, we showed that CBZ significantly enhances the autophagic flux in the APPswe/PS1deltaE9 mice which is unlikely via mTOR-dependent autophagy pathway. These data suggest that long-term CBZ treatment may have a protective effect in AD mouse model possibly through enhancing the autophagic flux.

 

3. Autophagy Enhancer Carbamazepine Alleviates Memory Deficits and Cerebral Amyloid-β Pathology in a Mouse Model of Alzheimer’s Disease

Author(s): Lixi Li, Sufang Zhang, Xin Zhang, Ting Li, Yu Tang, Hui Liu, Wendi Yang and Weidong Le

Affiliation: Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.

Abstract

Autophagy plays an important role in Alzheimer’s disease (AD). It has been reported that autophagic flux is altered in patients with AD, and application of the autophagy enhancer rapamycin may alleviate the cognitive impairment and amyloid-β (Aβ) neuropathology in transgenic animal model of AD. Since rapamycin is also an immune suppressor, there is a concern that long-term use of rapamycin may bring severe unwanted side effects. The aim of this study is to test if carbamazepine (CBZ), an anti-epileptic drug that has a potent autophagy enhancement effect, has anti-AD effects in APPswe/PS1deltaE9 transgenic mice model of AD. We found that APPswe/PS1deltaE9 mice display increased autophagic activity accompanied by decreased mTOR activity. After three months treatment with CBZ in the APPswe/PS1deltaE9 mice, we demonstrated that the spatial learning and memory deficits in these mice are significantly alleviated. We also documented that the cerebral amyloid plaque burden and Aβ42 levels in these mice are significantly reduced. Furthermore, we showed that CBZ significantly enhances the autophagic flux in the APPswe/PS1deltaE9 mice which is unlikely via mTOR-dependent autophagy pathway. These data suggest that long-term CBZ treatment may have a protective effect in AD mouse model possibly through enhancing the autophagic flux.

 
For more details on the journal, please visit: Current Alzheimer Research

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