2003 Fiscal Year Final Research Report Summary
Mechanism of the nerve cell death accompanied with tau protein phosphorylation in tauopathy
| Project/Area Number |
14570922
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Psychiatric science
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
TANAKA Toshihisa Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 講師 (10294068)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KAMINO Kouzin Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (40307955)
KUDO Takashi Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (10273632)
TAKEDA Masatoshi Osaka University Graduate School of Medicine, Professor, 医学系研究科, 教授 (00179649)
OKOCHI Masayasu Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (90335357)
|
|---|
| Project Period (FY) |
2002 – 2003
|
| Keywords | Alzheimer disease / tau Protein / neuronal cell death / tauopathy / double stranded RNA / neurofibilliary tangles / 神経細胞死 |
|---|
| Research Abstract |
Neurofibrillary tangles (NFTs) are neuropathological hallmarks of Alzheimer disease (AD) and abnormally hyperphosphorylated tau is the major. protein component of NFTs. Accumulation of hyperphosphorylated tau protein is also observed in other neurodegenerative diseases including subacute sclerosing panencephaltis (SSPE), and SSPE is caused by infection with measles RNA virus. Polyinosinic-polycytidylic acid (Poly(I ; C)), synthetic double stranded RNA (dsRNA), has been often used to make virus-infected cell models. We previously reported that tau protein phosphorylation in cells, was induced by dsRNA through TLR3 activation.
In this study effects of dsRNA was examined on microtubule-polymerization by tau and self-polymerization of tau, because tau is a negative-charged protein that has a similar character as gulucosaminoglycans including heparin. In binding assay poly(I ; C) was bound with *combinant GST-Staufen Δ tub which was a typical dsRNA binding protein lacking tubulin-binding domain, or tau protein, but not with actin or tubulin. Next, the polymerization of the microtubule was examined in the presence and absence of 0.2mg/ml of Poly(I ; C), and it was found that confirmed that the polymerization of the microtubule decreased remarkably in the presence of Poly(I ; C). When tau (1.6mg/mi) and Poly(LC) (0.8mg/ml) were mixed and incubated for 48 hours at 37℃, the electron microscopic study showed there were straight fibers (20-3Onm diameter).
It was suggested that dsRNA outside of neuronal cells induced tau protein phosphorylation through TLR activation and that dsRNA inside of neuronal cells disturbed the microtubule polymerization and promoted filament formations of tau protein.
Polyinosinic-polycytidylic acid (pI-pC), synthetic
|
