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Feasibility of β-sheet breaker peptide-H102 treatment for Alzheimer's disease based on β-amyloid hypothesis.

Lin LX, Bo XY, Tan YZ, Sun FX, Song M, Zhao J, Ma ZH, Li M, Zheng KJ, Xu SM - PLoS ONE (2014)

Bottom Line: This hypothesis claims that aggregation and neurotoxic effects of amyloid β (Aβ) is the common pathway in a variety of etiological factors for Alzheimer's disease.Based on the stereochemical structure of Aβ1-42 and aggregation character, we had designed a series of β-sheet breaker peptides in our previous work and screened out a 10-residue peptide β-sheet breaker peptide, H102.This study aims to validate the β-amyloid hypothesis and provide an experimental evidence for the feasibility of H102 treatment for Alzheimer's disease.

View Article: PubMed Central - PubMed

Affiliation: 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Key Laboratory of Hormone and Development (Ministry of Health), Metabolic Diseases Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.

ABSTRACT
β-amyloid hypothesis is the predominant hypothesis in the study of pathogenesis of Alzheimer's disease. This hypothesis claims that aggregation and neurotoxic effects of amyloid β (Aβ) is the common pathway in a variety of etiological factors for Alzheimer's disease. Aβ peptide derives from amyloid precursor protein (APP). β-sheet breaker peptides can directly prevent and reverse protein misfolding and aggregation in conformational disorders. Based on the stereochemical structure of Aβ1-42 and aggregation character, we had designed a series of β-sheet breaker peptides in our previous work and screened out a 10-residue peptide β-sheet breaker peptide, H102. We evaluated the effects of H102 on expression of P-tau, several associated proteins, inflammatory factors and apoptosis factors, and examined the cognitive ability of APP transgenic mice by behavioral test. This study aims to validate the β-amyloid hypothesis and provide an experimental evidence for the feasibility of H102 treatment for Alzheimer's disease.

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Expression of Bcl-2 and Bax in cerebral cortex and hippocampal area.a: cerebral cortex; b: hippocampal. 1: control group; 2: model group; 3: H102 group (magnification ×400). A: Expression of Bax stained by IHC. B, C: Mean intensity of Bax and positive area of Bax. (**P<0.01, ▵▵P<0.01). D: Expression of Bcl-2 stained by IHC. E, F: Mean intensity of Bcl-2 and positive area of Bcl-2 (**P<0.01). G: The ratio of Bcl-2/Bax (<0.01). H, I: Expression of Bcl-2 and Bax by Western blotting (<0.01). Error bars represent mean ± SEM. Statistical analysis was performed using one-way ANOVA following Student-Newman-Keuls test.
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pone-0112052-g004: Expression of Bcl-2 and Bax in cerebral cortex and hippocampal area.a: cerebral cortex; b: hippocampal. 1: control group; 2: model group; 3: H102 group (magnification ×400). A: Expression of Bax stained by IHC. B, C: Mean intensity of Bax and positive area of Bax. (**P<0.01, ▵▵P<0.01). D: Expression of Bcl-2 stained by IHC. E, F: Mean intensity of Bcl-2 and positive area of Bcl-2 (**P<0.01). G: The ratio of Bcl-2/Bax (<0.01). H, I: Expression of Bcl-2 and Bax by Western blotting (<0.01). Error bars represent mean ± SEM. Statistical analysis was performed using one-way ANOVA following Student-Newman-Keuls test.

Mentions: By Bax immunohistochemical staining, the positive cells in the cortex and hippocampus CA3 area were decreased in H102 group compared with model group (P<0.01), and there was no significant difference between control group and H102 group. In Bcl-2 immunohistochemical staining, positive cells in the cortex and hippocampus CA3 area were increased in H102 group (P<0.01) compared with model group, and there was no significant difference between control group and H102 group. As shown in Fig. 4G, compared with model group, the ratio of Bcl-2/Bax was obviously increased in H102 group (P<0.01), and there was no significant difference between control group and H102 group.


Feasibility of β-sheet breaker peptide-H102 treatment for Alzheimer's disease based on β-amyloid hypothesis.

Lin LX, Bo XY, Tan YZ, Sun FX, Song M, Zhao J, Ma ZH, Li M, Zheng KJ, Xu SM - PLoS ONE (2014)

Expression of Bcl-2 and Bax in cerebral cortex and hippocampal area.a: cerebral cortex; b: hippocampal. 1: control group; 2: model group; 3: H102 group (magnification ×400). A: Expression of Bax stained by IHC. B, C: Mean intensity of Bax and positive area of Bax. (**P<0.01, ▵▵P<0.01). D: Expression of Bcl-2 stained by IHC. E, F: Mean intensity of Bcl-2 and positive area of Bcl-2 (**P<0.01). G: The ratio of Bcl-2/Bax (<0.01). H, I: Expression of Bcl-2 and Bax by Western blotting (<0.01). Error bars represent mean ± SEM. Statistical analysis was performed using one-way ANOVA following Student-Newman-Keuls test.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4221228&req=5

pone-0112052-g004: Expression of Bcl-2 and Bax in cerebral cortex and hippocampal area.a: cerebral cortex; b: hippocampal. 1: control group; 2: model group; 3: H102 group (magnification ×400). A: Expression of Bax stained by IHC. B, C: Mean intensity of Bax and positive area of Bax. (**P<0.01, ▵▵P<0.01). D: Expression of Bcl-2 stained by IHC. E, F: Mean intensity of Bcl-2 and positive area of Bcl-2 (**P<0.01). G: The ratio of Bcl-2/Bax (<0.01). H, I: Expression of Bcl-2 and Bax by Western blotting (<0.01). Error bars represent mean ± SEM. Statistical analysis was performed using one-way ANOVA following Student-Newman-Keuls test.
Mentions: By Bax immunohistochemical staining, the positive cells in the cortex and hippocampus CA3 area were decreased in H102 group compared with model group (P<0.01), and there was no significant difference between control group and H102 group. In Bcl-2 immunohistochemical staining, positive cells in the cortex and hippocampus CA3 area were increased in H102 group (P<0.01) compared with model group, and there was no significant difference between control group and H102 group. As shown in Fig. 4G, compared with model group, the ratio of Bcl-2/Bax was obviously increased in H102 group (P<0.01), and there was no significant difference between control group and H102 group.

Bottom Line: This hypothesis claims that aggregation and neurotoxic effects of amyloid β (Aβ) is the common pathway in a variety of etiological factors for Alzheimer's disease.Based on the stereochemical structure of Aβ1-42 and aggregation character, we had designed a series of β-sheet breaker peptides in our previous work and screened out a 10-residue peptide β-sheet breaker peptide, H102.This study aims to validate the β-amyloid hypothesis and provide an experimental evidence for the feasibility of H102 treatment for Alzheimer's disease.

View Article: PubMed Central - PubMed

Affiliation: 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Key Laboratory of Hormone and Development (Ministry of Health), Metabolic Diseases Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.

ABSTRACT
β-amyloid hypothesis is the predominant hypothesis in the study of pathogenesis of Alzheimer's disease. This hypothesis claims that aggregation and neurotoxic effects of amyloid β (Aβ) is the common pathway in a variety of etiological factors for Alzheimer's disease. Aβ peptide derives from amyloid precursor protein (APP). β-sheet breaker peptides can directly prevent and reverse protein misfolding and aggregation in conformational disorders. Based on the stereochemical structure of Aβ1-42 and aggregation character, we had designed a series of β-sheet breaker peptides in our previous work and screened out a 10-residue peptide β-sheet breaker peptide, H102. We evaluated the effects of H102 on expression of P-tau, several associated proteins, inflammatory factors and apoptosis factors, and examined the cognitive ability of APP transgenic mice by behavioral test. This study aims to validate the β-amyloid hypothesis and provide an experimental evidence for the feasibility of H102 treatment for Alzheimer's disease.

Show MeSH
Related in: MedlinePlus