Lib, transcriptionally induced in senile plaque-associated astrocytes, promotes glial migration through extracellular matrix.
In an effort to identify astrocyte-derived molecules that may be intimately associated with progression of Alzheimer's disease (AD), Lib, a type I transmembrane protein belonging to leucine-rich repeat superfamily, has been identified as a distinctly inducible gene, responsive to beta-amyloid as well as pro-inflammatory cytokines in astrocytes. To evaluate the roles of Lib in AD, we investigated Lib expression in AD brain. In non-AD brain, Lib mRNA has been detected in neurons but not in quiescent astrocytes. On the contrary, in AD brain, Lib mRNA is expressed in activated astrocytes associated with senile plaques, but not expressed in neurons around lesions. Lib-expressing glioma cells displayed promotion of migration ability through reconstituted extracellular matrix and recombinant Lib protein bound to constituents of extracellular matrix. These observations suggest that Lib may contribute to regulation of cell-matrix adhesion interactions with respect to astrocyte recruitment around senile plaques in AD brain.
Satoh
Kazuki
K
The Fifth Frontier Project, Daiichi Pharmaceutical Co., Ltd., Tokyo 134-8640, Japan. satohj7i@daiichipharm.com.jp
Hata
Mitsumi
M
Shimizu
Tomoko
T
Yokota
Hiroshi
H
Akatsu
Hiroyasu
H
Yamamoto
Takayuki
T
Kosaka
Kenji
K
Yamada
Tatsuo
T
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D016022:Case-Control Studies; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D007930:Leucine / Q000737:chemistry; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry* / Q000502:physiology*; D008875:Middle Aged; D009457:Neuroglia / Q000166:cytology*; D009474:Neurons / Q000378:metabolism; D058225:Plaque, Amyloid / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D014158:Transcription, Genetic; D014162:Transfection
C446297:LRRC15 protein, human; D008565:Membrane Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D007930:Leucine