Project/Area Number |
09835010
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
老化(加齢)
|
Research Institution | Kumamoto University |
Principal Investigator |
KIMURA Takemi Kumamoto University・Hospital attached to Medical School, Assistant, 医学部・附属病院, 助手 (50284766)
|
Co-Investigator(Kenkyū-buntansha) |
HORIUCHI Seikoh Kumamoto University・Medical School, Professor, 医学部, 教授 (10117377)
MIYAKAWA Taihei Kumamoto University・Medical School, Professor, 医学部, 教授 (90040542)
|
Project Period (FY) |
1997 – 1998
|
Project Status |
Completed (Fiscal Year 1998)
|
Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1997: ¥1,400,000 (Direct Cost: ¥1,400,000)
|
Keywords | advanced glycation end products (AGE) / N^<epsilon>- (carboxymethyl) lysine / pentosidine / receptor for AGE / galectin-3 / astrocytes / aging / dementia / galectin-3 / advanced glycation and products(AGE) / astrocyte / amyloid β protein / Alzheimer's disease / advanced glycation and products / 封入体 / アルツハイマー病 / ピック病 |
Research Abstract |
N^<epsilon>-(carboxymethyl)lysine and pentosidine that are structures of advanced glycation end products (AGE) were immunohistochemically found in brain age dependent inclusions such as lipofuscin granules and corpora amylacca and in dementia related abnormal structures including Pick's bodies, ballooned neurons, and Lewy bodies but not in neurofibrillary tangles. As such AGE-structures have been considered to be glycoxidation products, glycation and oxidation may play a important role in pathogenesis in aging and some diseases leading dementia. RAGE, one of receptors for AGE, was reportedly associated with formation of brain lesions in Alzheimer's disease (AD). Here, in order to clarify a link between galectin-3, the other AGE-receptor, and AD, we examined AD and non-demented brains using immunological methods. In this immunoblotting experiment, a galectin-3-positive band was observed in brains from AD patients and a part of non-demented aged controls but not in young brains. Immunohistochemically, galectin-3 as well as N^<epsilon>-(carboxymethyl)lysine and pentosidine were detected in reactive astrocytes and senile plaques with gliosis. Our con-focal laser scanning microscopy showed a localization of galectin-3 in astrocytic elements within senile plaques. These findings suggest that in aging and AD, galectin-3-positive astrocytes phagocytose and degrade AGE and astrocytes further-activated by AGE are involved in formation and/or maturation of senile plaques.
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