Therapeutic immunization protects dopaminergic neurons in a mouse model of Parkinson's disease

被引：242

作者：

Benner, EJ

Mosley, RL

Destache, CJ

Lewis, TB

Jackson-Lewis, V

Gorantla, S

Nemachek, C

Green, SR

Przedborski, S

Gendelman, HE

机构：

[1] Univ Nebraska, Med Ctr, Ctr Neurovirol & Neurodegenerat Disorders, Omaha, NE 68198 USA

[2] Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA

[3] Univ Nebraska, Med Ctr, Dept Internal Med, Omaha, NE 68198 USA

[4] Columbia Univ, Dept Neurol, New York, NY 10032 USA

[5] Columbia Univ, Dept Pathol, New York, NY 10032 USA

[6] Columbia Univ, Ctr Neurobiol & Behav, New York, NY 10032 USA

[7] Creighton Univ, Coll Pharm, Omaha, NE 68178 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2004年 / 101卷 / 25期

关键词：

D O I：

10.1073/pnas.0400569101

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Degeneration of the nigrostriatal dopaminergic pathway, the hallmark of Parkinson's disease, can be recapitulated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mice. Herein, we demonstrate that adoptive transfer of copolymer-1 immune cells to MPTP recipient mice leads to T cell accumulation within the substantial nigra pars compacta, suppression of microglial activation, and increased local expression of astrocyte-associated glial cell line-derived neurotrophic factor. This immunization strategy resulted in significant protection of nigrostriatal neurons against MPTP-induced neurodegeneration that was abrogated by depletion of donor T cells. Such vaccine treatment strategies may provide benefit for Parkinson's disease.

引用

页码：9435 / 9440

页数：6

共 43 条

[1] Specific Th2 cells accumulate in the central nervous system of mice protected against experimental autoimmune encephalomyelitis by copolymer 1 [J].