Indole and synthetic derivative activate chaperone expression to reduce polyQ aggregation in SCA17 neuronal cell and slice culture models

Pin Jui Kung, Yu Chen Tao, Ho Chiang Hsu, Wan Ling Chen, Te Hsien Lin, Donala Janreddy, Ching Fa Yao, Kuo Hsuan Chang, Jung Yaw Lin, Ming Tsan Su, Chung Hsin Wu, Guey Jen Lee-Chen, Hsiu Mei Hsieh-Li

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

In spinocerebellar ataxia type 17 (SCA17), the expansion of a translated CAG repeat in the TATA box binding protein (TBP) gene results in a long polyglutamine (polyQ) tract in the TBP protein, leading to intracellular accumulation of aggregated TBP and cell death. The molecular chaperones act in preventing protein aggregation to ameliorate downstream harmful events. In this study, we used Tet-On SH-SY5Y cells with inducible SCA17 TBP/Q79-green fluorescent protein (GFP) expression to test indole and synthetic derivative NC001-8 for neuroprotection. We found that indole and NC001-8 up-regulated chaperone expression to reduce polyQ aggregation in neuronal differentiated TBP/Q79 cells. The effects on promoting neurite outgrowth and on reduction of aggregation on Purkinje cells were also confirmed with cerebellar primary and slice cultures of SCA17 transgenic mice. Our results demonstrate how indole and derivative NC001-8 reduce polyQ aggregation to support their therapeutic potentials in SCA17 treatment.

Original languageEnglish
Pages (from-to)1929-1939
Number of pages11
JournalDrug Design, Development and Therapy
Volume8
DOIs
Publication statusPublished - 2014 Oct 16

Fingerprint

TATA-Box Binding Protein
Cell Culture Techniques
Molecular Chaperones
Purkinje Cells
Green Fluorescent Proteins
Transgenic Mice
Proteins
Cell Death
Spinocerebellar Ataxia 17
indole
polyglutamine
Genes

Keywords

  • Indole and derivative
  • PolyQ aggregation
  • Spinocerebellar ataxia type 17
  • TATA box binding protein
  • Therapeutics

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery

Cite this

Indole and synthetic derivative activate chaperone expression to reduce polyQ aggregation in SCA17 neuronal cell and slice culture models. / Kung, Pin Jui; Tao, Yu Chen; Hsu, Ho Chiang; Chen, Wan Ling; Lin, Te Hsien; Janreddy, Donala; Yao, Ching Fa; Chang, Kuo Hsuan; Lin, Jung Yaw; Su, Ming Tsan; Wu, Chung Hsin; Lee-Chen, Guey Jen; Hsieh-Li, Hsiu Mei.

In: Drug Design, Development and Therapy, Vol. 8, 16.10.2014, p. 1929-1939.

Research output: Contribution to journalArticle

@article{f5d9dd2524334d25b26ca460cbea6abd,
title = "Indole and synthetic derivative activate chaperone expression to reduce polyQ aggregation in SCA17 neuronal cell and slice culture models",
abstract = "In spinocerebellar ataxia type 17 (SCA17), the expansion of a translated CAG repeat in the TATA box binding protein (TBP) gene results in a long polyglutamine (polyQ) tract in the TBP protein, leading to intracellular accumulation of aggregated TBP and cell death. The molecular chaperones act in preventing protein aggregation to ameliorate downstream harmful events. In this study, we used Tet-On SH-SY5Y cells with inducible SCA17 TBP/Q79-green fluorescent protein (GFP) expression to test indole and synthetic derivative NC001-8 for neuroprotection. We found that indole and NC001-8 up-regulated chaperone expression to reduce polyQ aggregation in neuronal differentiated TBP/Q79 cells. The effects on promoting neurite outgrowth and on reduction of aggregation on Purkinje cells were also confirmed with cerebellar primary and slice cultures of SCA17 transgenic mice. Our results demonstrate how indole and derivative NC001-8 reduce polyQ aggregation to support their therapeutic potentials in SCA17 treatment.",
keywords = "Indole and derivative, PolyQ aggregation, Spinocerebellar ataxia type 17, TATA box binding protein, Therapeutics",
author = "Kung, {Pin Jui} and Tao, {Yu Chen} and Hsu, {Ho Chiang} and Chen, {Wan Ling} and Lin, {Te Hsien} and Donala Janreddy and Yao, {Ching Fa} and Chang, {Kuo Hsuan} and Lin, {Jung Yaw} and Su, {Ming Tsan} and Wu, {Chung Hsin} and Lee-Chen, {Guey Jen} and Hsieh-Li, {Hsiu Mei}",
year = "2014",
month = "10",
day = "16",
doi = "10.2147/DDDT.S67376",
language = "English",
volume = "8",
pages = "1929--1939",
journal = "Drug Design, Development and Therapy",
issn = "1177-8881",
publisher = "Dove Medical Press Ltd.",

}

TY - JOUR

T1 - Indole and synthetic derivative activate chaperone expression to reduce polyQ aggregation in SCA17 neuronal cell and slice culture models

AU - Kung, Pin Jui

AU - Tao, Yu Chen

AU - Hsu, Ho Chiang

AU - Chen, Wan Ling

AU - Lin, Te Hsien

AU - Janreddy, Donala

AU - Yao, Ching Fa

AU - Chang, Kuo Hsuan

AU - Lin, Jung Yaw

AU - Su, Ming Tsan

AU - Wu, Chung Hsin

AU - Lee-Chen, Guey Jen

AU - Hsieh-Li, Hsiu Mei

PY - 2014/10/16

Y1 - 2014/10/16

N2 - In spinocerebellar ataxia type 17 (SCA17), the expansion of a translated CAG repeat in the TATA box binding protein (TBP) gene results in a long polyglutamine (polyQ) tract in the TBP protein, leading to intracellular accumulation of aggregated TBP and cell death. The molecular chaperones act in preventing protein aggregation to ameliorate downstream harmful events. In this study, we used Tet-On SH-SY5Y cells with inducible SCA17 TBP/Q79-green fluorescent protein (GFP) expression to test indole and synthetic derivative NC001-8 for neuroprotection. We found that indole and NC001-8 up-regulated chaperone expression to reduce polyQ aggregation in neuronal differentiated TBP/Q79 cells. The effects on promoting neurite outgrowth and on reduction of aggregation on Purkinje cells were also confirmed with cerebellar primary and slice cultures of SCA17 transgenic mice. Our results demonstrate how indole and derivative NC001-8 reduce polyQ aggregation to support their therapeutic potentials in SCA17 treatment.

AB - In spinocerebellar ataxia type 17 (SCA17), the expansion of a translated CAG repeat in the TATA box binding protein (TBP) gene results in a long polyglutamine (polyQ) tract in the TBP protein, leading to intracellular accumulation of aggregated TBP and cell death. The molecular chaperones act in preventing protein aggregation to ameliorate downstream harmful events. In this study, we used Tet-On SH-SY5Y cells with inducible SCA17 TBP/Q79-green fluorescent protein (GFP) expression to test indole and synthetic derivative NC001-8 for neuroprotection. We found that indole and NC001-8 up-regulated chaperone expression to reduce polyQ aggregation in neuronal differentiated TBP/Q79 cells. The effects on promoting neurite outgrowth and on reduction of aggregation on Purkinje cells were also confirmed with cerebellar primary and slice cultures of SCA17 transgenic mice. Our results demonstrate how indole and derivative NC001-8 reduce polyQ aggregation to support their therapeutic potentials in SCA17 treatment.

KW - Indole and derivative

KW - PolyQ aggregation

KW - Spinocerebellar ataxia type 17

KW - TATA box binding protein

KW - Therapeutics

UR - http://www.scopus.com/inward/record.url?scp=84908062029&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84908062029&partnerID=8YFLogxK

U2 - 10.2147/DDDT.S67376

DO - 10.2147/DDDT.S67376

M3 - Article

C2 - 25342886

AN - SCOPUS:84908062029

VL - 8

SP - 1929

EP - 1939

JO - Drug Design, Development and Therapy

JF - Drug Design, Development and Therapy

SN - 1177-8881

ER -