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Medical Microbiology and Immunology : Volume 205

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Remarkable reductions of PAKs in the brain tissues of scrapie-infected rodent possibly linked closely with neuron loss

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Remarkable reductions of PAKs in the brain tissues of scrapie-infected rodent possibly linked closely with neuron loss

Content Provider	Springer Nature Link
Author	Meng, Ge Tian, Chan Wang, Hui Xu, Yin Zhang, Bao Yun Shi, Qi Gao, Chen Chen, Cao Fan, Xue Yu Wang, Jing Xiao, Kang Ren, Ke Xue, Ming Ming Dong, Xiao Ping
Copyright Year	2014
Abstract	Prion diseases are irreversible progressive neurodegenerative diseases characterized in the brain by PrPSc deposits, neuronal degeneration, gliosis and by cognitive, behavioral and physical impairments, leading to severe incapacity and inevitable death. Proteins of the p21-activated kinase (PAK) family are noted for roles in gene transcription, cytoskeletal dynamics, cell cycle progression and survival signaling. In the present study, we aimed to identify the potential roles of PAKs during prion infection, utilizing the brains of scrapie agent-infected hamsters. Western blots and immunohistochemical assays showed that brain levels of PAK3 and PAK1, as well as their upstream activator Rac/cdc42 and downstream substrate Raf1, were remarkably reduced at terminal stage. Double-stained immunofluorescent assay demonstrated that PAK3 was expressed mainly in neurons. Dynamic analyses of the brain samples collected at the different time points during the incubation period illustrated successive decreases of PAK3, PAK1 and Raf1, especially phosphor Raf1, which correlated well with neuron loss. Rac/cdc42 in the brain tissues increased at early stage and reached to the top at mid–late stage, but diminished at final stage. Unlike the alteration of PAKs in vivo, PAK3 and PAK1, as well as Rac/cdc42 and Raf1 in the prion-infected cell line SMB-S15 remained unchanged compared with those of its normal cell line SMB-PS. Our data here indicate that the functions of PAKs and their associated signaling pathways are seriously affected in the brains of prion disease, which appear to associate closely with the extensive neuron loss.
Starting Page	291
Ending Page	302
Page Count	12
File Format	PDF
ISSN	03008584
Journal	Medical Microbiology and Immunology
Volume Number	203
Issue Number	5
e-ISSN	14321831
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2014-05-29
Publisher Place	Berlin/Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Prion Scrapie PAKs Rac/cdc42 Raf1 Medical Microbiology Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology Microbiology (medical)

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Remarkable reductions of PAKs in the brain tissues of scrapie-infected rodent possibly linked closely with neuron loss

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