Open AccessBAG1 Over‐expression in Brain Protects Against Stroke
Author(s) -
Kermer Pawel,
Digicaylioglu Murat H.,
Kaul Marcus,
Zapata Juan M.,
Krajewska Maryla,
StennerLiewen Frank,
Takayama Shinichi,
Krajewski Stanistan,
Lipton Stuart A.,
Reed John C.
Publication year - 2003
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/j.1750-3639.2003.tb00480.x
Subject(s) - neuroprotection , genetically modified mouse , heat shock protein , transgene , in vivo , hsp70 , apoptosis , biology , glutamate receptor , programmed cell death , stroke (engine) , microbiology and biotechnology , central nervous system , neuroscience , pharmacology , medicine , gene , biochemistry , receptor , genetics , mechanical engineering , engineering
The co‐chaperone BAG1 binds and regulates 70 kDa heat shock proteins (Hsp70/Hsc70) and exhibits cytoprotective activity in cell culture models. Recently, we observed that BAG1 expression is induced during neuronal differentiation in the developing brain. However, the in vivo effects of BAG1 during development and after maturation of the central nervous system have never been examined. We generated transgenic mice over‐expressing BAG1 in neurons. While brain development was essentially normal, cultured cortical neurons from transgenic animals exhibited resistance to glutamate‐induced, apoptotic neuronal death. Moreover, in an in vivo stroke model involving transient middle cerebral artery occlusion, BAG1 transgenic mice demonstrated decreased mortality and substantially reduced infarct volumes compared to wild‐type littermates. Interestingly, brain tissue from BAG1 transgenic mice contained higher levels of neuroprotective Hsp70/Hsc70 protein but not mRNA, suggesting a potential mechanism whereby BAG1 exerts its anti‐apoptotic effects. In summary, BAG1 displays potent neuroprotective activity in vivo against stroke, and therefore represents an interesting target for developing new therapeutic strategies including gene therapy and small‐molecule drugs for reducing brain injury during cerebral ischemia and neurodegenerative diseases.