A Drosophila model of mutant human parkin-induced toxicity demonstrates selective loss of dopaminergic neurons and dependence on cellular dopamine

被引：105

作者：

Sang, Tzu-Kang

Chang, Hui-Yun

Lawless, George M.

Ratnaparkhi, Anuradha

Mee, Lisa

Ackerson, Larry C.

Maidment, Nigel T.

Krantz, David E.

Jackson, George R.

机构：

[1] Natl Tsing Hua Univ, Dept Neurol, Neurogenet Program, Hsinchu, Taiwan

[2] Natl Tsing Hua Univ, Dept Neurol, Movement Disorders Program, Hsinchu, Taiwan

[3] Natl Tsing Hua Univ, Inst Biotechnol, Hsinchu, Taiwan

[4] Natl Tsing Hua Univ, Dept Life Sci, Hsinchu, Taiwan

[5] Univ Calif Los Angeles, Gonda Goldschmied Neurosci & Genet Res Ctr, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA

[6] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA

[7] Univ Calif Los Angeles, Hatos Ctr Neuropharmacol, Los Angeles, CA 90095 USA

[8] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Ctr Neurobehav Genet, Los Angeles, CA 90095 USA

来源：

JOURNAL OF NEUROSCIENCE | 2007年 / 27卷 / 05期

关键词：

dopaminergic; Drosophila; monoamine; aging (ageing); neuroprotection; neuronal death; RECESSIVE JUVENILE PARKINSONISM; PSEUDO-DOMINANT INHERITANCE; UBIQUITIN-PROTEIN LIGASE; TARGETED GENE-EXPRESSION; EARLY-ONSET PARKINSONISM; ALPHA-SYNUCLEIN; TYROSINE-HYDROXYLASE; ASYMPTOMATIC CARRIERS; INCLUSION FORMATION; PROTECTIVE FUNCTION;

D O I：

10.1523/JNEUROSCI.4810-06.2007

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Mutations in human parkin have been identified in familial Parkinson's disease and in some sporadic cases. Here, we report that expression of mutant but not wild-type human parkin in Drosophila causes age-dependent, selective degeneration of dopaminergic (DA) neurons accompanied by a progressive motor impairment. Overexpression or knockdown of the Drosophila vesicular monoamine transporter, which regulates cytosolic DA homeostasis, partially rescues or exacerbates, respectively, the degenerative phenotypes caused by mutant human parkin. These results support a model in which the vulnerability of DA neurons to parkin-induced neurotoxicity results from the interaction of mutant parkin with cytoplasmic dopamine.

引用

页码：981 / 992

页数：12

共 112 条

[91] Intraneuronal dopamine-quinone synthesis: A review [J].

Sulzer, David ;

Zecca, Luigi .

NEUROTOXICITY RESEARCH, 1999, 1 (03) :181-195

[92] Influence of heterozygosity for Parkin mutation on onset age in familial Parkinson disease : The GenePD study [J].

Sun, Mei ;

Latourelle, Jeanne C. ;

Wooten, Frederick ;

Lew, Mark F. ;

Klein, Christine ;

Shill, Holly A. ;

Golbe, Lawrence I. ;

Mark, Margery H. ;

Racette, Brad A. ;

Perlmutter, Joel S. ;

Parsian, Abbas ;

Guttman, Mark ;

Nicholson, Garth ;

Xu, Gang ;

Wilk, Jemma B. ;

Saint-Hilaire, Marie H. ;

DeStefano, Anita L. ;

Prakash, Ranjana ;

Williamson, Sally ;

Suchowersky, Oksana ;

Labelle, Nancy ;

Growdon, John H. ;

Singer, Carlos ;

Watts, Ray L. ;

Goldwurm, Stefano ;

Pezzoli, Gianni ;

Baker, Kenneth B. ;

Pramstaller, Peter P. ;

Burn, David J. ;

Chinnery, Patrick F. ;

Sherman, Scott ;

Vieregge, Peter ;

Litvan, Irene ;

Gillis, Tammy ;

MacDonald, Marcy E. ;

Myers, Richard H. ;

Gusella, James F. .

ARCHIVES OF NEUROLOGY, 2006, 63 (06) :826-832

[93] VMAT2 knockout mice: Heterozygotes display reduced amphetamine-conditioned reward, enhanced amphetamine locomotion, and enhanced MPTP toxicity [J].

Takahashi, N ;

Miner, LL ;

Sora, I ;

Ujike, H ;

Revay, RS ;

Kostic, V ;

JacksonLewis, V ;

Przedborski, S ;

Uhl, GR .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (18) :9938-9943

[94] Marked variation in clinical presentation and age of onset in a family with a heterozygous parkin mutation [J].

Tan, LC ;

Tanner, CM ;

Chen, R ;

Chan, P ;

Farrer, M ;

Hardy, J ;

Langston, JW .

MOVEMENT DISORDERS, 2003, 18 (07) :758-763

[95] Neuronal overexpression of APPL, the Drosophila homologue of the amyloid precursor protein (APP), disrupts axonal transport [J].

Torroja, L ;

Chu, H ;

Kotovsky, I ;

White, K .

CURRENT BIOLOGY, 1999, 9 (09) :489-492

[96] The degeneration of dopamine neurons in Parkinson's disease insights from embryology and evolution of the mesostriatocortical system [J].

Vernier, P ;

Moret, F ;

Callier, S ;

Snapyan, M ;

Wersinger, C ;

Sidhu, A .

PROTECTIVE STRATEGIES FOR NEURODEGENERATIVE DISEASES, 2004, 1035 :231-249

[97] Loss of locus coeruleus neurons and reduced startle in parkin null mice [J].

von Coelln, R ;

Thomas, B ;

Savitt, JM ;

Lim, KL ;

Sasaki, M ;

Hess, EJ ;

Dawson, VL ;

Dawson, TM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (29) :10744-10749

[98] Stress-induced alterations in parkin solubility promote parkin aggregation and compromise parkin's protective function [J].

Wang, C ;

Ko, HS ;

Thomas, B ;

Tsang, F ;

Chew, KCM ;

Tay, SP ;

Ho, MWL ;

Lim, TM ;

Soong, TW ;

Pletnikova, O ;

Troncoso, J ;

Dawson, VL ;

Dawson, TM ;

Lim, KL .

HUMAN MOLECULAR GENETICS, 2005, 14 (24) :3885-3897

[99] Alterations in the solubility and intracellular localization of parkin by several familial Parkinson's disease-linked point mutations [J].

Wang, C ;

Tan, JMM ;

Ho, MWL ;

Zaiden, N ;

Wong, SH ;

Chew, CLC ;

Eng, PW ;

Lim, TM ;

Dawson, TM ;

Lim, KL .

JOURNAL OF NEUROCHEMISTRY, 2005, 93 (02) :422-431

[100] Two-photon calcium imaging reveals an odor-evoked map of activity in the fly brain [J].

Wang, JW ;

Wong, AM ;

Flores, J ;

Vosshall, LB ;

Axel, R .

CELL, 2003, 112 (02) :271-282

← 3 4 5 6 7 8 9 10 11 12 →