Transforming growth factor beta2 autocrinally mediates neuronal cell death induced by amyloid-beta.
Amyloid beta (Abeta), the major component of the senile plaques of Alzheimer's disease, is implicated in neuronal cell death. We have found that Abeta42, a neurotoxic form of Abeta peptide, induces both neuronal and glial expression of TGFbeta2. We have further demonstrated that the addition into culture media of neutralizing antibody to TGFbeta2 or a large amount of the recombinant soluble amyloid precursor protein alpha, the extracellular domain of amyloid precursor protein (APP) generated by alpha secretase, suppresses death in primary cortical neurons (PCNs) induced by Abeta42 in vitro. Combined with the finding in our recent study indicating that TGFbeta2 is a neuronal cell death-inducing ligand for APP, it is suggested that TGFbeta2 is an autocrinal mediator for Abeta42-induced death in PCNs.
Hashimoto
Yuichi
Y
Department of Pharmacology, KEIO University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Nawa
Mikiro
M
Chiba
Tomohiro
T
Aiso
Sadakazu
S
Nishimoto
Ikuo
I
Matsuoka
Masaaki
M
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D002540:Cerebral Cortex / Q000166:cytology; D004347:Drug Interactions; D004622:Embryo, Mammalian; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D005910:Glioma; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects*; D010446:Peptide Fragments / Q000633:toxicity*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D053781:Transforming Growth Factor beta2
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C509041:TGFB2 protein, human; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; C075222:amyloid beta-protein (1-42)