Sushi repeat-containing protein 1: a novel disease-associated molecule in cerebral amyloid angiopathy.
Acta Neuropathol
; 134(4): 605-617, 2017 Oct.
Article
en En
| MEDLINE
| ID: mdl-28478503
Sporadic cerebral amyloid angiopathy (CAA) is characterized by cerebrovascular amyloid beta (Aß) deposits and causes cerebral hemorrhage and dementia. The exact molecules that co-accumulate with cerebrovascular Aß deposits are still not fully known. In our study here, we performed proteomic analyses with microdissected leptomeningeal arteries and cerebral neocortical arterioles from 8 cases with severe CAA, 12 cases with mild CAA, and 10 control cases without CAA, and we determined the levels of highly expressed proteins in cerebral blood vessels in CAA. We focused on sushi repeat-containing protein 1 (SRPX1), which is specifically expressed in CAA-affected cerebral blood vessels. Because SRPX1, which is known as a tumor suppressor gene, reportedly induced apoptosis in tumor cells, we hypothesized that SRPX1 may play an important role in Aß-induced apoptosis in CAA. Immunohistochemical studies revealed that SRPX1 co-accumulated with Aß deposits in cerebral blood vessels of all autopsied cases with severe CAA. In contrast, no SRPX1 co-accumulated with Aß deposits in senile plaques. Furthermore, we demonstrated that both Aß40 and Aß42 bound to SRPX1 in vitro and enhanced SRPX1 expression in primary cultures of cerebrovascular smooth muscle cells. SRPX1 enhanced caspase activity induced by Aß40. Knockdown of SRPX1, in contrast, reduced the formation of Aß40 accumulations and the activity of caspase in cultured cerebrovascular smooth muscle cells. SRPX1 may thus be a novel molecule that is up-regulated in cerebrovascular Aß deposits and that may increase Aß-induced cerebrovascular degeneration in CAA.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Encéfalo
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Angiopatía Amiloide Cerebral
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Proteínas de la Membrana
Tipo de estudio:
Risk_factors_studies
Límite:
Aged
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Aged80
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Acta Neuropathol
Año:
2017
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Alemania