Mouse model of multiple system atrophy α-synuclein expression in oligodendrocytes causes glial and neuronal degeneration

被引：238

作者：

Yazawa, I

Giasson, BI

Sasaki, R

Zhang, B

Joyce, S

Uryu, K

Trojanowski, JQ

Lee, VMY ^{[1
]}

机构：

[1] Univ Penn, Sch Med, Ctr Neurodegenerat Dis Res, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

[2] Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA

[3] Univ Penn, Sch Med, Inst Aging, Philadelphia, PA 19104 USA

来源：

NEURON | 2005年 / 45卷 / 06期

关键词：

D O I：

10.1016/j.neuron.2005.01.032

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Transgenic (Tg) mice overexpressing human wild-type alpha-synuclein in oligodendrocytes under the control of the 2,' 3'-cyclic nucleotide X-phosphodiesterase (CNP) promoter are shown here to recapitulate features of multiple system atrophy (MSA), including the accumulation of filamentous human alpha-synuclein aggregates in oligodendrocytes linked to their degeneration and autophagocytosis of myelin. Significantly, endogenous mouse (x-synuclein also accumulated in normal and degenerating axons and axon terminals in association with oligodendroglia and neuron loss and slowly progressive motor impairments. Our studies demonstrate that overexpression of alpha-synuclein in oligodendrocytes of mice results in MSA-like degeneration in the CNS and that a-synuclein inclusions in oligodendrocytes participate in the degeneration of neurons in MSA.

引用

页码：847 / 859

页数：13

共 44 条

[1] NACP/α-synuclein immunoreactivity in fibrillary components of neuronal and oligodendroglial cytoplasmic inclusions in the pontine nuclei in multiple system atrophy [J].

Arima, K ;

Uéda, K ;

Sunohara, N ;

Arakawa, K ;

Hirai, S ;

Nakamura, M ;

Tonozuka-Uehara, H ;

Kawai, M .

ACTA NEUROPATHOLOGICA, 1998, 96 (05) :439-444

[2]

Baba M, 1998, AM J PATHOL, V152, P879

[3] CONNEXIN MUTATIONS IN X-LINKED CHARCOT-MARIE-TOOTH DISEASE [J].

BERGOFFEN, J ;

SCHERER, SS ;

WANG, S ;

SCOTT, MO ;

BONE, LJ ;

PAUL, DL ;

CHEN, K ;

LENSCH, MW ;

CHANCE, PF ;

FISCHBECK, KH .

SCIENCE, 1993, 262 (5142) :2039-2042

[4] Wild-type nonneuronal cells extend survival of SOD1 mutant motor neurons in ALS mice [J].

Clement, AM ;

Nguyen, MD ;

Roberts, EA ;

Garcia, ML ;

Boillée, S ;

Rule, M ;

McMahon, AP ;

Doucette, W ;

Siwek, D ;

Ferrante, RJ ;

Brown, RH ;

Julien, JP ;

Goldstein, LSB ;

Cleveland, DW .

SCIENCE, 2003, 302 (5642) :113-117

[5] Widespread alterations of α-synuclein in multiple system atrophy [J].

Dickson, DW ;

Liu, WK ;

Hardy, J ;

Farrer, M ;

Mehta, N ;

Uitti, R ;

Mark, M ;

Zimmerman, T ;

Golbe, L ;

Sage, J ;

Sima, A ;

D'Amato, C ;

Albin, R ;

Gilman, S ;

Yen, SH .

AMERICAN JOURNAL OF PATHOLOGY, 1999, 155 (04) :1241-1251

[6] Immunohistochemical and biochemical studies demonstrate a distinct profile of α-synuclein permutations in multiple system atrophy [J].

Duda, JE ;

Giasson, BI ;

Gur, TL ;

Montine, TJ ;

Robertson, D ;

Biaggioni, I ;

Hurtig, HI ;

Stern, MB ;

Gollomp, SM ;

Grossman, M ;

Lee, VMY ;

Trojanowski, JQ .

JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2000, 59 (09) :830-841

[7]

Duda JE, 2000, J NEUROSCI RES, V61, P121, DOI 10.1002/1097-4547(20000715)61:2<121::AID-JNR1>3.0.CO

[8]

2-4

[9] CHARACTERIZATION OF A NOVEL PROTEIN REGULATED DURING THE CRITICAL PERIOD FOR SONG LEARNING IN THE ZEBRA FINCH [J].

GEORGE, JM ;

JIN, H ;

WOODS, WS ;

CLAYTON, DF .

NEURON, 1995, 15 (02) :361-372

[10] Initiation and synergistic fibrillization of tau and alpha-synuclein [J].

Giasson, BI ;

Forman, MS ;

Higuchi, M ;

Golbe, LI ;

Graves, CL ;

Kotzbauer, PT ;

Trojanowski, JQ ;

Lee, VMY .

SCIENCE, 2003, 300 (5619) :636-640

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