Ganglioside Hp-s1 Analogue Inhibits Amyloidogenic Toxicity in Alzheimer's Disease Model Cells

Yow Fu Tsai, Dun Jhu Yang, Thi Huong Ngo, Cheng Hua Shih, Yu Fa Wu, Ching Kuo Lee, Veerapol Phraekanjanavichid, Shu Fen Yen, Shu Huei Kao, Horng Mo Lee, Vivian Shuhsien Huang, Jonathan Chang Cheng Shieh, Yung Feng Lin

研究成果: 雜誌貢獻文章

1 引文 (Scopus)

摘要

Alzheimer's disease (AD) is characterized by extracellular deposition of amyloid plaques, which are predominantly composed of amyloid-β (Aβ) peptide derived from amyloid precursor protein (APP) cleavage. APP interacts with tropomyosin receptor kinase A, a neurotrophic receptor associated with gangliosides and mediating neuronal survival and differentiation through the extracellular signal-regulated protein kinase (ERK) pathway. The ganglioside Hp-s1's analogue Hp-s1A exerts neuritogenic activity; however, its effect on AD pathology remains unknown. To test the hypothesis that Hp-s1A is a potential candidate to treat AD, we established the AD-modeled cell line by expressing human Swedish and Indiana APP gene (APP-Swe/Ind) in N2a mouse neuroblastoma cells. The cells were treated with Hp-s1A or monosialoganglioside GM1 for comparison. The AD model cells expressing APP-Swe/Ind exhibited a significant reduction in viability, as well as neurite outgrowth rate, in comparison to the control cells expressing APP-695. APP C-terminal fragment-β (CTFβ) and Aβ42 were increased in the AD cell lysates and the culture media, respectively. With the treatment of either Hp-s1A or GM1 at 1 μM, the AD model cells showed a significant increase in viability; however, only Hp-s1A reduced CTFβ levels in these cells. Further analysis of the culture media revealed that Hp-s1A also reduced Aβ42 production from AD model cells. The phosphorylation of ERK was elevated and the neurite outgrowth rate was restored with Hp-s1A treatment. In conclusion, the ganglioside analogue Hp-s1A inhibited amyloidogenic processing of APP and promoted neurotrophic activity and survival of AD model cells. Hp-s1A has great potential in AD therapeutic development.
原文英語
頁(從 - 到)528-536
頁數9
期刊ACS Chemical Neuroscience
10
發行號1
DOIs
出版狀態已發佈 - 一月 16 2019

指紋

Gangliosides
Amyloid beta-Protein Precursor
Toxicity
Alzheimer Disease
Cells
Amyloid
Culture Media
MAP Kinase Signaling System
Tropomyosin
Extracellular Signal-Regulated MAP Kinases
Amyloid Plaques
Phosphorylation
Protein C
Neuroblastoma
Pathology
Protein Kinases
Cell Culture Techniques
Phosphotransferases
Genes
Cell Line

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cognitive Neuroscience
  • Cell Biology

引用此文

Ganglioside Hp-s1 Analogue Inhibits Amyloidogenic Toxicity in Alzheimer's Disease Model Cells. / Tsai, Yow Fu; Yang, Dun Jhu; Ngo, Thi Huong; Shih, Cheng Hua; Wu, Yu Fa; Lee, Ching Kuo; Phraekanjanavichid, Veerapol; Yen, Shu Fen; Kao, Shu Huei; Lee, Horng Mo; Huang, Vivian Shuhsien; Shieh, Jonathan Chang Cheng; Lin, Yung Feng.

於: ACS Chemical Neuroscience, 卷 10, 編號 1, 16.01.2019, p. 528-536.

研究成果: 雜誌貢獻文章

Tsai, YF, Yang, DJ, Ngo, TH, Shih, CH, Wu, YF, Lee, CK, Phraekanjanavichid, V, Yen, SF, Kao, SH, Lee, HM, Huang, VS, Shieh, JCC & Lin, YF 2019, 'Ganglioside Hp-s1 Analogue Inhibits Amyloidogenic Toxicity in Alzheimer's Disease Model Cells', ACS Chemical Neuroscience, 卷 10, 編號 1, 頁 528-536. https://doi.org/10.1021/acschemneuro.8b00406
Tsai, Yow Fu ; Yang, Dun Jhu ; Ngo, Thi Huong ; Shih, Cheng Hua ; Wu, Yu Fa ; Lee, Ching Kuo ; Phraekanjanavichid, Veerapol ; Yen, Shu Fen ; Kao, Shu Huei ; Lee, Horng Mo ; Huang, Vivian Shuhsien ; Shieh, Jonathan Chang Cheng ; Lin, Yung Feng. / Ganglioside Hp-s1 Analogue Inhibits Amyloidogenic Toxicity in Alzheimer's Disease Model Cells. 於: ACS Chemical Neuroscience. 2019 ; 卷 10, 編號 1. 頁 528-536.
@article{9b9e5efd10f14688a639ce18bad8400e,
title = "Ganglioside Hp-s1 Analogue Inhibits Amyloidogenic Toxicity in Alzheimer's Disease Model Cells",
abstract = "Alzheimer's disease (AD) is characterized by extracellular deposition of amyloid plaques, which are predominantly composed of amyloid-β (Aβ) peptide derived from amyloid precursor protein (APP) cleavage. APP interacts with tropomyosin receptor kinase A, a neurotrophic receptor associated with gangliosides and mediating neuronal survival and differentiation through the extracellular signal-regulated protein kinase (ERK) pathway. The ganglioside Hp-s1's analogue Hp-s1A exerts neuritogenic activity; however, its effect on AD pathology remains unknown. To test the hypothesis that Hp-s1A is a potential candidate to treat AD, we established the AD-modeled cell line by expressing human Swedish and Indiana APP gene (APP-Swe/Ind) in N2a mouse neuroblastoma cells. The cells were treated with Hp-s1A or monosialoganglioside GM1 for comparison. The AD model cells expressing APP-Swe/Ind exhibited a significant reduction in viability, as well as neurite outgrowth rate, in comparison to the control cells expressing APP-695. APP C-terminal fragment-β (CTFβ) and Aβ42 were increased in the AD cell lysates and the culture media, respectively. With the treatment of either Hp-s1A or GM1 at 1 μM, the AD model cells showed a significant increase in viability; however, only Hp-s1A reduced CTFβ levels in these cells. Further analysis of the culture media revealed that Hp-s1A also reduced Aβ42 production from AD model cells. The phosphorylation of ERK was elevated and the neurite outgrowth rate was restored with Hp-s1A treatment. In conclusion, the ganglioside analogue Hp-s1A inhibited amyloidogenic processing of APP and promoted neurotrophic activity and survival of AD model cells. Hp-s1A has great potential in AD therapeutic development.",
keywords = "Alzheimer's disease, amyloid precursor protein, amyloid-β, amyloidogenesis, ganglioside, Hp-s1, Hp-s1A, neuritogenesis, neurotrophic signaling",
author = "Tsai, {Yow Fu} and Yang, {Dun Jhu} and Ngo, {Thi Huong} and Shih, {Cheng Hua} and Wu, {Yu Fa} and Lee, {Ching Kuo} and Veerapol Phraekanjanavichid and Yen, {Shu Fen} and Kao, {Shu Huei} and Lee, {Horng Mo} and Huang, {Vivian Shuhsien} and Shieh, {Jonathan Chang Cheng} and Lin, {Yung Feng}",
year = "2019",
month = "1",
day = "16",
doi = "10.1021/acschemneuro.8b00406",
language = "English",
volume = "10",
pages = "528--536",
journal = "ACS Chemical Neuroscience",
issn = "1948-7193",
publisher = "American Chemical Society",
number = "1",

}

TY - JOUR

T1 - Ganglioside Hp-s1 Analogue Inhibits Amyloidogenic Toxicity in Alzheimer's Disease Model Cells

AU - Tsai, Yow Fu

AU - Yang, Dun Jhu

AU - Ngo, Thi Huong

AU - Shih, Cheng Hua

AU - Wu, Yu Fa

AU - Lee, Ching Kuo

AU - Phraekanjanavichid, Veerapol

AU - Yen, Shu Fen

AU - Kao, Shu Huei

AU - Lee, Horng Mo

AU - Huang, Vivian Shuhsien

AU - Shieh, Jonathan Chang Cheng

AU - Lin, Yung Feng

PY - 2019/1/16

Y1 - 2019/1/16

N2 - Alzheimer's disease (AD) is characterized by extracellular deposition of amyloid plaques, which are predominantly composed of amyloid-β (Aβ) peptide derived from amyloid precursor protein (APP) cleavage. APP interacts with tropomyosin receptor kinase A, a neurotrophic receptor associated with gangliosides and mediating neuronal survival and differentiation through the extracellular signal-regulated protein kinase (ERK) pathway. The ganglioside Hp-s1's analogue Hp-s1A exerts neuritogenic activity; however, its effect on AD pathology remains unknown. To test the hypothesis that Hp-s1A is a potential candidate to treat AD, we established the AD-modeled cell line by expressing human Swedish and Indiana APP gene (APP-Swe/Ind) in N2a mouse neuroblastoma cells. The cells were treated with Hp-s1A or monosialoganglioside GM1 for comparison. The AD model cells expressing APP-Swe/Ind exhibited a significant reduction in viability, as well as neurite outgrowth rate, in comparison to the control cells expressing APP-695. APP C-terminal fragment-β (CTFβ) and Aβ42 were increased in the AD cell lysates and the culture media, respectively. With the treatment of either Hp-s1A or GM1 at 1 μM, the AD model cells showed a significant increase in viability; however, only Hp-s1A reduced CTFβ levels in these cells. Further analysis of the culture media revealed that Hp-s1A also reduced Aβ42 production from AD model cells. The phosphorylation of ERK was elevated and the neurite outgrowth rate was restored with Hp-s1A treatment. In conclusion, the ganglioside analogue Hp-s1A inhibited amyloidogenic processing of APP and promoted neurotrophic activity and survival of AD model cells. Hp-s1A has great potential in AD therapeutic development.

AB - Alzheimer's disease (AD) is characterized by extracellular deposition of amyloid plaques, which are predominantly composed of amyloid-β (Aβ) peptide derived from amyloid precursor protein (APP) cleavage. APP interacts with tropomyosin receptor kinase A, a neurotrophic receptor associated with gangliosides and mediating neuronal survival and differentiation through the extracellular signal-regulated protein kinase (ERK) pathway. The ganglioside Hp-s1's analogue Hp-s1A exerts neuritogenic activity; however, its effect on AD pathology remains unknown. To test the hypothesis that Hp-s1A is a potential candidate to treat AD, we established the AD-modeled cell line by expressing human Swedish and Indiana APP gene (APP-Swe/Ind) in N2a mouse neuroblastoma cells. The cells were treated with Hp-s1A or monosialoganglioside GM1 for comparison. The AD model cells expressing APP-Swe/Ind exhibited a significant reduction in viability, as well as neurite outgrowth rate, in comparison to the control cells expressing APP-695. APP C-terminal fragment-β (CTFβ) and Aβ42 were increased in the AD cell lysates and the culture media, respectively. With the treatment of either Hp-s1A or GM1 at 1 μM, the AD model cells showed a significant increase in viability; however, only Hp-s1A reduced CTFβ levels in these cells. Further analysis of the culture media revealed that Hp-s1A also reduced Aβ42 production from AD model cells. The phosphorylation of ERK was elevated and the neurite outgrowth rate was restored with Hp-s1A treatment. In conclusion, the ganglioside analogue Hp-s1A inhibited amyloidogenic processing of APP and promoted neurotrophic activity and survival of AD model cells. Hp-s1A has great potential in AD therapeutic development.

KW - Alzheimer's disease

KW - amyloid precursor protein

KW - amyloid-β

KW - amyloidogenesis

KW - ganglioside

KW - Hp-s1

KW - Hp-s1A

KW - neuritogenesis

KW - neurotrophic signaling

UR - http://www.scopus.com/inward/record.url?scp=85056135572&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85056135572&partnerID=8YFLogxK

U2 - 10.1021/acschemneuro.8b00406

DO - 10.1021/acschemneuro.8b00406

M3 - Article

AN - SCOPUS:85056135572

VL - 10

SP - 528

EP - 536

JO - ACS Chemical Neuroscience

JF - ACS Chemical Neuroscience

SN - 1948-7193

IS - 1

ER -