PROLYL OLIGOPEPTIDASE COLOCALIZES WITH α-SYNUCLEIN, β-AMYLOID, TAU PROTEIN AND ASTROGLIA IN THE POST-MORTEM BRAIN SAMPLES WITH PARKINSON'S AND ALZHEIMER'S DISEASES
PROLYL OLIGOPEPTIDASE COLOCALIZES WITH α-SYNUCLEIN, β-AMYLOID, TAU PROTEIN AND ASTROGLIA IN THE POST-MORTEM BRAIN SAMPLES WITH PARKINSON'S AND ALZHEIMER'S DISEASES
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DOI：
10.1016/j.neuroscience.2013.03.049
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发表时间：
2013-07-09
期刊：
影响因子：
3.3
通讯作者：
Garcia-Horsman, J. A.
中科院分区：
文献类型：
--
作者：
Hannula, M. J.;Myohanen, T. T.;Garcia-Horsman, J. A.
脯氨酰寡肽酶（EC 3.4.21.26，PREP）是一种丝氨酸蛋白酶，可水解短于 30 聚体的含脯氨酸肽，但它也具有非水解功能。 PREP 已被证明可以在无细胞条件下加速野生型 α-突触核蛋白 (α-syn) 的聚集，而 PREP 抑制剂可以在体外和体内阻断这种聚集。 a-syn是帕金森病（PD）和路易体痴呆症中路易体的主要成分。为了阐明 PREP 与神经退行性疾病其他标志物可能存在的相互作用，我们研究了 PD、阿尔茨海默病 (AD) 患者死后脑样本和健康对照脑样本中 PREP 与 (1) a-syn、(2) p-淀粉样蛋白、(3) tau 蛋白和 (4) 星形胶质细胞和小胶质细胞的共定位。在 PD 大脑的黑质中，与 PREP 和 a-syn 的强烈共定位是明显的。 PREP 还与 AD 大脑中的 p-淀粉样斑块以及 AD 和健康大脑中的 tau 蛋白共定位。 PREP 也在 PD、AD 和对照大脑的星形胶质细胞中发现，但在小胶质细胞中没有发现。我们的研究结果首次证明了 PREP 和病理蛋白在人脑中的共定位，并支持了这样的观点：至少在空间方面，PREP 可能与神经退行性疾病的发病机制有关。 (C) 2013 国际广播组织。由爱思唯尔有限公司出版。保留所有权利。
Prolyl oligopeptidase (EC 3.4.21.26, PREP) is a serine protease that hydrolyzes proline-containing peptides shorter than 30-mer but it has also nonhydrolytic functions. PREP has been shown to accelerate aggregation of wildtype a-synuclein (alpha-syn) under cell-free conditions, and PREP inhibitors can block this aggregation both in vitro and in vivo. a-syn is the main component of Lewy bodies in Parkinson's disease (PD) and Lewy body dementia. To clarify the possible interaction of PREP with other markers of neurodegenerative diseases, we studied colocalizations of PREP and (1) a-syn, (2) p-amyloid, (3) tau protein and (4) astroglial and microglial cells in human post-mortem brain samples from PD, Alzheimer's disease (AD) patients and in healthy control brain samples. In the substantia nigra of PD brains, an intense colocalization with PREP and a-syn was evident. PREP colocalized also with p-amyloid plaques in AD brains and with tau protein in AD and in healthy brains. PREP was also found in astroglial cells in PD, AD and control brains, but not in the microglia. Our findings are the first ones to demonstrate colocalization of PREP and pathological proteins in the human brain and support the view that, at least in spatial terms, PREP could be associated with pathogenesis of neurodegenerative diseases. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.