A multifunctional peptide rescues memory deficits in Alzheimer's disease transgenic mice by inhibiting Aβ42-induced cytotoxicity and increasing microglial phagocytosis
Alzheimer's disease (AD) is characterized by progressive memory loss due to extracellular senile plaques and intracellular neurofibrillary tangles. The toxic β-amyloid (Aβ) aggregates that form in AD can induce the overproduction of reactive oxygen species (ROS), nitric oxide (NO), and proinfla...
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| Format: | Article |
| Language: | English |
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Elsevier
2012-06-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996112000848 |
| _version_ | 1818573896437202944 |
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| author | Di Xue Min Zhao Yu-jiong Wang Li Wang Yang Yang Shao-wei Wang Ran Zhang Yang Zhao Rui-tian Liu |
| author_facet | Di Xue Min Zhao Yu-jiong Wang Li Wang Yang Yang Shao-wei Wang Ran Zhang Yang Zhao Rui-tian Liu |
| author_sort | Di Xue |
| collection | DOAJ |
| description | Alzheimer's disease (AD) is characterized by progressive memory loss due to extracellular senile plaques and intracellular neurofibrillary tangles. The toxic β-amyloid (Aβ) aggregates that form in AD can induce the overproduction of reactive oxygen species (ROS), nitric oxide (NO), and proinflammatory cytokines. These Aβ aggregates likely play a pivotal role in the onset and progression of AD. Reducing Aβ generation, inhibiting Aβ toxicity, and improving Aβ clearance are promising therapeutic strategies for AD. The present paper is the first to reveal a heptapeptide (XD4) isolated from a Ph.D.-C7C library through phage display that significantly inhibited Aβ cytotoxicity, increased the microglial phagocytosis of Aβ, decreased the Aβ-induced generation of ROS and NO, and attenuated the disequilibrium of calcium homeostasis in vitro. Remarkably, XD4 also attenuated memory deficits in β-amyloid precursor protein/presenilin 1 (APPswe/PS1dE9) transgenic mice, and reduced amyloid plaque burden and Aβ40/42 levels. The results of the present study indicate that this peptide, which specifically targets Aβ, may be a promising new therapy for patients exhibiting cognitive impairment and increased Aβ burden. |
| first_indexed | 2024-12-15T00:19:02Z |
| format | Article |
| id | doaj.art-5e0edf9718be492aa962edcd299e9110 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-15T00:19:02Z |
| publishDate | 2012-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-5e0edf9718be492aa962edcd299e91102022-12-21T22:42:22ZengElsevierNeurobiology of Disease1095-953X2012-06-01463701709A multifunctional peptide rescues memory deficits in Alzheimer's disease transgenic mice by inhibiting Aβ42-induced cytotoxicity and increasing microglial phagocytosisDi Xue0Min Zhao1Yu-jiong Wang2Li Wang3Yang Yang4Shao-wei Wang5Ran Zhang6Yang Zhao7Rui-tian Liu8Tsinghua University School of Medicine, Haidian District, Beijing 100084, China; School of Life Science, Ningxia University, Yinchuan 750021, ChinaTsinghua University School of Medicine, Haidian District, Beijing 100084, ChinaSchool of Life Science, Ningxia University, Yinchuan 750021, ChinaTsinghua University School of Medicine, Haidian District, Beijing 100084, ChinaTsinghua University School of Medicine, Haidian District, Beijing 100084, China; School of Life Science, Ningxia University, Yinchuan 750021, ChinaTsinghua University School of Medicine, Haidian District, Beijing 100084, ChinaTsinghua University School of Medicine, Haidian District, Beijing 100084, China; School of Life Science, Ningxia University, Yinchuan 750021, ChinaDivision of Recombinant Technology Products, National Institutes for Food and Drug Control, Beijing 100050, China; Correspondence to: Y. Zhao, Division of Recombinant Technology Products, National Institutes for Food and Drug Control, Beijing 100050, China.Tsinghua University School of Medicine, Haidian District, Beijing 100084, China; Corresponding author. Fax: +86 10 62792995.Alzheimer's disease (AD) is characterized by progressive memory loss due to extracellular senile plaques and intracellular neurofibrillary tangles. The toxic β-amyloid (Aβ) aggregates that form in AD can induce the overproduction of reactive oxygen species (ROS), nitric oxide (NO), and proinflammatory cytokines. These Aβ aggregates likely play a pivotal role in the onset and progression of AD. Reducing Aβ generation, inhibiting Aβ toxicity, and improving Aβ clearance are promising therapeutic strategies for AD. The present paper is the first to reveal a heptapeptide (XD4) isolated from a Ph.D.-C7C library through phage display that significantly inhibited Aβ cytotoxicity, increased the microglial phagocytosis of Aβ, decreased the Aβ-induced generation of ROS and NO, and attenuated the disequilibrium of calcium homeostasis in vitro. Remarkably, XD4 also attenuated memory deficits in β-amyloid precursor protein/presenilin 1 (APPswe/PS1dE9) transgenic mice, and reduced amyloid plaque burden and Aβ40/42 levels. The results of the present study indicate that this peptide, which specifically targets Aβ, may be a promising new therapy for patients exhibiting cognitive impairment and increased Aβ burden.http://www.sciencedirect.com/science/article/pii/S0969996112000848Alzheimer's diseaseβ-AmyloidPeptideCytotoxicityMemory deficitsAβ clearance |
| spellingShingle | Di Xue Min Zhao Yu-jiong Wang Li Wang Yang Yang Shao-wei Wang Ran Zhang Yang Zhao Rui-tian Liu A multifunctional peptide rescues memory deficits in Alzheimer's disease transgenic mice by inhibiting Aβ42-induced cytotoxicity and increasing microglial phagocytosis Neurobiology of Disease Alzheimer's disease β-Amyloid Peptide Cytotoxicity Memory deficits Aβ clearance |
| title | A multifunctional peptide rescues memory deficits in Alzheimer's disease transgenic mice by inhibiting Aβ42-induced cytotoxicity and increasing microglial phagocytosis |
| title_full | A multifunctional peptide rescues memory deficits in Alzheimer's disease transgenic mice by inhibiting Aβ42-induced cytotoxicity and increasing microglial phagocytosis |
| title_fullStr | A multifunctional peptide rescues memory deficits in Alzheimer's disease transgenic mice by inhibiting Aβ42-induced cytotoxicity and increasing microglial phagocytosis |
| title_full_unstemmed | A multifunctional peptide rescues memory deficits in Alzheimer's disease transgenic mice by inhibiting Aβ42-induced cytotoxicity and increasing microglial phagocytosis |
| title_short | A multifunctional peptide rescues memory deficits in Alzheimer's disease transgenic mice by inhibiting Aβ42-induced cytotoxicity and increasing microglial phagocytosis |
| title_sort | multifunctional peptide rescues memory deficits in alzheimer s disease transgenic mice by inhibiting aβ42 induced cytotoxicity and increasing microglial phagocytosis |
| topic | Alzheimer's disease β-Amyloid Peptide Cytotoxicity Memory deficits Aβ clearance |
| url | http://www.sciencedirect.com/science/article/pii/S0969996112000848 |
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