Neuronal Store-Operated Calcium Entry Pathway as a Novel Therapeutic Target for Huntington's Disease Treatment

被引：131

作者：

Wu, Jun ^{[1
]}

Shih, Hsin-Pei ^{[2
]}

Vigont, Vladimir ^{[3
]}

Hrdlicka, Lori ^{[2
]}

Diggins, Len ^{[2
]}

Singh, Carol ^{[2
]}

Mahoney, Matt ^{[2
]}

Chesworth, Richard ^{[2
]}

Shapiro, Gideon ^{[2
]}

Zimina, Olga ^{[3
]}

Chen, Xuesong ^{[1
]}

Wu, Qingqing ^{[1
]}

Glushankova, Lyubov ^{[3
]}

Ahlijanian, Michael ^{[2
]}

Koenig, Gerhard ^{[2
]}

Mozhayeva, Galina N. ^{[3
]}

Kaznacheyeva, Elena ^{[3
]}

Bezprozvanny, Ilya ^{[1
]}

机构：

[1] UT SW Med Ctr, Dept Physiol, Dallas, TX 75390 USA

[2] EnVivo Pharmaceut, Watertown, MA 02472 USA

[3] Russian Acad Sci, Inst Cytol, St Petersburg 194064, Russia

来源：

CHEMISTRY & BIOLOGY | 2011年 / 18卷 / 06期

关键词：

KAPPA-B ACTIVATION; AMYLOID PRECURSOR PROTEIN; CAPACITATIVE CA2+ ENTRY; MOUSE MODEL; MUTANT HUNTINGTIN; STRIATAL NEURONS; RAT STRIATUM; 2-AMINOETHOXYDIPHENYL BORATE; POTENT INHIBITORS; INDUCED APOPTOSIS;

D O I：

10.1016/j.chembiol.2011.04.012

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Huntington's disease (HD) is a neurodegenerative disorder caused by a polyglutamine expansion within Huntingtin (Htt) protein. In the phenotypic screen we identified a class of quinazoline-derived compounds that delayed a progression of a motor phenotype in transgenic Drosophila HD flies. We found that the store-operated calcium (Ca(2+)) entry (SOC) pathway activity is enhanced in neuronal cells expressing mutant Htt and that the identified compounds inhibit SOC pathway in HD neurons. The same compounds exerted neuroprotective effects in glutamate-toxicity assays with YAC128 medium spiny neurons primary cultures. We demonstrated a key role of TRPC1 channels in supporting SOC pathway in HD neurons. We concluded that the TRPC1-mediated neuronal SOC pathway constitutes a novel target for HD treatment and that the identified compounds represent a novel class of therapeutic agents for treatment of HD and possibly other neurodegenerative disorders.

引用

收藏

页码：777 / 793

页数：17

相关论文

共 72 条

[1]

CHIP protects from the neurotoxicity of expanded and wild-type ataxin-1 and promotes their ubiquitination and degradation [J].

Al-Ramahi, Ismael ;

Lam, Yung C. ;

Chen, Hung-Kai ;

de Gouyon, Beatrice ;

Zhang, Minghang ;

Perez, Alma M. ;

Branco, Joana ;

de Haro, Maria ;

Patterson, Cam ;

Zoghbi, Huda Y. ;

Botas, Juan .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (36) :26714-26724

[2]

ALRAMAHI I, 2010, SOC NEUR SAN DIEG CA

[3]

Alterations in the ankyrin domain of TRPV4 cause congenital distal SMA, scapuloperoneal SMA and HMSN2C [J].

Auer-Grumbach, Michaela ;

Olschewski, Andrea ;

Papic, Lea ;

Kremer, Hannie ;

McEntagart, Meriel E. ;

Uhrig, Sabine ;

Fischer, Carina ;

Froehlich, Eleonore ;

Balint, Zoltan ;

Tang, Bi ;

Strohmaier, Heimo ;

Lochmueller, Hanns ;

Schlotter-Weigel, Beate ;

Senderek, Jan ;

Krebs, Angelika ;

Dick, Katherine J. ;

Petty, Richard ;

Longman, Cheryl ;

Anderson, Neil E. ;

Padberg, George W. ;

Schelhaas, Helenius J. ;

van Ravenswaaij-Arts, Conny M. A. ;

Pieber, Thomas R. ;

Crosby, Andrew H. ;

Guelly, Christian .

NATURE GENETICS, 2010, 42 (02) :160-U96

[4]

Formation of a new receptor-operated channel by heteromeric assembly of TRPP2 and TRPC1 subunits [J].

Bai, Chang-Xi ;

Giamarchi, Aurelie ;

Rodat-Despoix, Lise ;

Padilla, Francoise ;

Downs, Tamyra ;

Tsiokas, Leonidas ;

Delmas, Patrick .

EMBO REPORTS, 2008, 9 (05) :472-479

[5]

A point mutation in TRPC3 causes abnormal Purkinje cell development and cerebellar ataxia in moonwalker mice [J].

Becker, Esther B. E. ;

Olivera, Peter L. ;

Glitsch, Maike D. ;

Banks, Gareth T. ;

Achilli, Francesca ;

Hardy, Andrea ;

Nolan, Patrick M. ;

Fisher, Elizabeth M. C. ;

Davies, Kay E. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (16) :6706-6711

[6]

STIM2 Regulates Capacitive Ca2+ Entry in Neurons and Plays a Key Role in Hypoxic Neuronal Cell Death [J].

Berna-Erro, Alejandro ;

Braun, Attila ;

Kraft, Robert ;

Kleinschnitz, Christoph ;

Schuhmann, Michael K. ;

Stegner, David ;

Wultsch, Thomas ;

Eilers, Jens ;

Meuth, Sven G. ;

Stoll, Guido ;

Nieswandt, Bernhard .

SCIENCE SIGNALING, 2009, 2 (93) :ra67

[7]

Calcium signaling and neurodegenerative diseases [J].

Bezprozvanny, Ilya .

TRENDS IN MOLECULAR MEDICINE, 2009, 15 (03) :89-100

[8]

TRPC1-mediated inhibition of 1-methyl-4-phenylpyridinium ion neurotoxicity in human SH-SY5Y neuroblastoma cells [J].

Bollimuntha, S ;

Singh, BB ;

Shavali, S ;

Sharma, SK ;

Ebadi, M .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (03) :2132-2140

[9]

2-Aminoethoxydiphenyl borate (2-APB) is a reliable blocker of store-operated Ca2+ entry but an inconsistent inhibitor of InsP3-induced Ca2+ release [J].

Bootman, MD ;

Collins, TJ ;

Mackenzie, L ;

Roderick, HL ;

Berridge, MJ ;

Peppiatt, CM .

FASEB JOURNAL, 2002, 16 (10) :1145-1150

[10]

BMS-345541 is a highly selective inhibitor of IκB kinase that binds at an allosteric site of the enzyme and blocks NF-κB-dependent transcription in mice [J].

Burke, JR ;

Pattoli, MA ;

Gregor, KR ;

Brassil, PJ ;

MacMaster, JF ;

McIntyre, KW ;

Yang, XX ;

Iotzova, VS ;

Clarke, W ;

Strnad, J ;

Qiu, YP ;

Zusi, FC .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (03) :1450-1456

← 1 2 3 4 5 6 7 8 →