Novel dot-blot assay for detection of vascular Notch3 aggregates in patients with CADASIL

被引:7
作者
Ma, Yihong [1 ]
Ueda, Mitsuharu [1 ]
Ueda, Akihiko [1 ]
Shinriki, Satoru [2 ]
Nagatoshi, Akihito [1 ,3 ]
Isoguchi, Aito [1 ]
Okada, Masamitsu [1 ]
Tasaki, Masayoshi [1 ,4 ]
Nomura, Toshiya [1 ]
Inoue, Yasuteru [1 ]
Masuda, Teruaki [1 ]
Misumi, Yohei [1 ]
Yamashita, Taro [1 ]
Matsui, Hirotaka [2 ]
Ando, Yukio [1 ,5 ]
机构
[1] Kumamoto Univ, Grad Sch Med Sci, Dept Neurol, 1-1-1 Honjo, Kumamoto 8600811, Japan
[2] Kumamoto Univ, Grad Sch Med Sci, Dept Mol Lab Med, Kumamoto 8600811, Japan
[3] Kumamoto Gen Hosp, Dept Neurol, Yatsushiro 8668660, Japan
[4] Kumamoto Univ, Grad Sch Hlth Sci, Dept Morphol & Physiol Sci, Kumamoto 8620976, Japan
[5] Nagasaki Int Univ, Dept Amyloidosis Res, Sasebo 8593298, Japan
基金
日本学术振兴会;
关键词
CADASIL; Dot-blot assay; Notch3; Biopsy; Diagnosis; AUTOSOMAL-DOMINANT ARTERIOPATHY; GRANULAR OSMIOPHILIC MATERIAL; SUBCORTICAL INFARCTS; LEUKOENCEPHALOPATHY; DISEASE;
D O I
10.1016/j.jns.2020.116931
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
To detect vascular Notch3 extracellular domain aggregates in CADASIL, we developed a novel dot-blot assay with both autopsy and biopsy skin samples. We obtained samples from 11 patients with CADASIL and 12 control patients, and we performed dot-blot analyses by using sequential biochemical tissue extractions with three different antibodies against specific regions of the Notch3 extracellular domain. We also analyzed clinical features and vascular accumulations of Notch3 by immunohistochemistry. Via the dot-blot assay with the antibody against the C-terminal region of the Notch3 extracellular domain, we successfully detected Notch3 extracellular domain aggregates in skin tissue homogenates obtained from patients with CADASIL. Our novel method may therefore aid the diagnosis of CADASIL.
引用
收藏
页数:5
相关论文
共 12 条
[1]   CADASIL [J].
Chabriat, Hugues ;
Joutel, Anne ;
Dichgans, Martin ;
Tournier-Lasserve, Elizabeth ;
Bousser, Marie-Germaine .
LANCET NEUROLOGY, 2009, 8 (07) :643-653
[2]   Role of NOTCH3 Mutations in the Cerebral Small Vessel Disease Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy [J].
Coupland, Kirsten ;
Lendahl, Urban ;
Karlstrom, Helena .
STROKE, 2018, 49 (11) :2793-2800
[3]  
FAZEKAS F, 1987, AM J NEURORADIOL, V8, P421
[4]   Pathophysiological Mechanisms and Potential Therapeutic Targets in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (CADASIL) [J].
Locatelli, Martina ;
Padovani, Alessandro ;
Pezzini, Alessandro .
FRONTIERS IN PHARMACOLOGY, 2020, 11
[5]   Notch and disease: A growing field [J].
Louvi, Angeliki ;
Artavanis-Tsakonas, Spyros .
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, 2012, 23 (04) :473-480
[6]   Abnormal recruitment of extracellular matrix proteins by excess Notch3ECD: a new pathomechanism in CADASIL [J].
Monet-Lepretre, Marie ;
Haddad, Iman ;
Baron-Menguy, Celine ;
Fouillot-Panchal, Mai ;
Riani, Meriem ;
Domenga-Denier, Valerie ;
Dussaule, Claire ;
Cognat, Emmanuel ;
Vinh, Joelle ;
Joutel, Anne .
BRAIN, 2013, 136 :1830-1845
[7]   MRI hyperintensities of the temporal lobe and external capsule in patients with CADASIL [J].
O'Sullivan, M ;
Jarosz, JM ;
Martin, RJ ;
Deasy, N ;
Powell, JF ;
Markus, HS .
NEUROLOGY, 2001, 56 (05) :628-634
[8]   The Cerebral Autosomal-Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (CADASIL) Scale A Screening Tool to Select Patients for NOTCH3 Gene Analysis [J].
Pescini, Francesca ;
Nannucci, Serena ;
Bertaccini, Bruno ;
Salvadori, Emilia ;
Bianchi, Silvia ;
Ragno, Michele ;
Sarti, Cristina ;
Valenti, Raffaella ;
Zicari, Enza ;
Moretti, Marco ;
Chiti, Stefano ;
Stromillo, Maria Laura ;
De Stefano, Nicola ;
Dotti, Maria Teresa ;
Federico, Antonio ;
Inzitari, Domenico ;
Pantoni, Leonardo .
STROKE, 2012, 43 (11) :2871-U167
[9]   Detection of granular osmiophilic material of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy by light microscopy in frozen sections [J].
Ueda, A. ;
Hirano, T. ;
Takahashi, K. ;
Kurisaki, R. ;
Hino, H. ;
Uyama, E. ;
Uchino, M. .
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, 2009, 35 (06) :618-622
[10]   Genotypic and phenotypic spectrum of CADASIL in Japan: the experience at a referral center in Kumamoto University from 1997 to 2014 [J].
Ueda, Akihiko ;
Ueda, Mitsuharu ;
Nagatoshi, Akihito ;
Hirano, Teruyuki ;
Ito, Takaaki ;
Arai, Nobutaka ;
Uyama, Eiichiro ;
Mori, Kota ;
Nakamura, Masaaki ;
Shinriki, Satoru ;
Ikeda, Katsuyoshi ;
Ando, Yukio .
JOURNAL OF NEUROLOGY, 2015, 262 (08) :1828-1836