Increase of adenomatous polyposis coli immunoreactivity is a marker of reactive astrocytes in Alzheimer's disease and in other pathological conditions

Increase of adenomatous polyposis coli immunoreactivity is a marker of reactive astrocytes in Alzheimer's disease and in other pathological conditions
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腺瘤性息肉病大肠杆菌免疫反应性的增加是阿尔茨海默病和其他病理状况中反应性星形胶质细胞的标志

DOI:
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发表时间:
2001
影响因子:
12.7
通讯作者:
J. Brion
J. Brion
中科院分区:
医学1区
文献类型:
--
作者:
K. Leroy;C. Duyckaerts;L. Bovekamp;O. Müller;B. Anderton;J. Brion

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抽象的。大肠腺瘤性息肉病(APC)肿瘤抑制基因的突变是家族性大肠腺瘤性息肉病和许多散发性结直肠肿瘤中结肠癌的原因。APC基因的产物也是正常发育所必需的,并在成人大脑中表达。我们研究了APC在正常人脑颞叶皮层和海马中的免疫细胞化学定位,在阿尔茨海默病(AD)和其他几种神经病理条件。APC在对照组和不同疾病患者的神经元胞体和树突中均有表达。此外,高APC表达中观察到的比例的星形胶质细胞和胶质细胞酸性蛋白阳性的星形胶质细胞在AD。此外,在AD中,与老年斑中β淀粉样蛋白(Aβ)沉积相关的星形胶质细胞中APC阳性星形胶质细胞的比例高于与Aβ沉积无关的星形胶质细胞。APC阳性星形胶质细胞也观察到在控制情况下,在弥漫性路易体病,克-雅氏病,艾滋病毒脑炎和周围脑梗死。毛细胞型星形细胞瘤和胶质母细胞瘤中的肿瘤星形细胞也呈强APC阳性。在培养的星形胶质细胞中未检测到APC。这些结果表明,APC表达上调星形胶质细胞激活后,由几种类型的病理性损伤,是一个新发现的分子特征的星形胶质细胞的反应性表型,可能与细胞增殖的控制。此外,它还表明Aβ和/或与Aβ沉积相关的炎症过程是AD中星形胶质细胞中APC表达优先增加的原因。
Abstract. Mutations in the adenomatous polyposis coli (APC) tumor suppressor gene are responsible for colon cancer in familial adenomatous polyposis coli and in many sporadic colorectal tumors. The product of the APC gene is also essential for normal development and is expressed in the adult brain. We have investigated the immunocytochemical localization of APC in the temporal cortex and hippocampus of normal human brain, in Alzheimer's disease (AD) and in several other neuropathological conditions. APC was expressed in neuronal cell bodies and dendrites both in control subjects and in patients with different diseases. In addition, a high APC expression was observed in a proportion of fibrillary and glial fibrillary acidic protein-positive astrocytes in AD. Furthermore, in AD the proportion of APC-positive astrocytes was higher in astrocytes associated with β-amyloid (Aβ) deposits in senile plaques than in astrocytes not associated to Aβ deposits. APC-positive astrocytes were also observed in control cases, in diffuse Lewy body disease, in Creutzfeldt-Jacob disease, in HIV encephalitis and around cerebral infarcts. Tumoral astrocytes in pilocytic astrocytoma and in glioblastoma were also strongly APC positive. APC was not detected in cultured astroglial cells. These results indicate that APC expression is up-regulated in astrocytes following their activation by several types of pathological insults and is a newly identified molecular characteristic of the reactive phenotype of astrocytes, possibly related to the control of cell proliferation. In addition, it also suggests that Aβ, and/or the inflammatory process associated with Aβ deposits, is responsible for a preferential increase of APC expression in astrocytes in AD.
APC 基因的选择性剪接及其与终末分化的关联。
DOI: --
发表时间: 1997
期刊: Cancer research.
影响因子: --
作者:
Santoro,IM;Groden,J
通讯作者: Groden,J
DOI: 10.1126/science.8259519
发表时间: 1993-12-10
期刊: SCIENCE
影响因子: 56.9
作者:
SU, LK;VOGELSTEIN, B;KINZLER, KW
通讯作者: KINZLER, KW