ライフサイエンスコーパス: CADASIL

1 CADASIL changes also induced aberrant homodimerization o

2 CADASIL is a genetic paradigm of cerebral small vessel d

3 CADASIL pathology is characterized by vascular smooth mu

4 CADASIL results from mutations in Notch3 that alter the

5 CADASIL, an inherited SVD, alters cerebral artery functi

6 hanced in mice expressing a vascular Notch 3 CADASIL mutation (R90C) or a Notch 3 knockout mutation.

7 uences of CADASIL mutations, we engineered 4 CADASIL-like mutations into rat Notch3 and have shown th

8 antibodies avidly stained arteries in 8 of 8 CADASIL brain samples.

9 chanism by which these mutations result in a CADASIL phenotype has been widely speculated upon.

10 ar domain in mice with the C455R mutation, a CADASIL variant associated with Notch3 loss of function.

11 All CADASIL mutations described to date affect the epidermal

12 ms in the cerebral vessels of North American CADASIL patients with classical NOTCH3 mutations.

13 o hereditary syndromes known as Alagille and CADASIL.

14 ner (SHP, NROB2) gene in normal subjects and CADASIL (cerebral autosomal dominant arteriopathy with s

15 h family with hereditary MID suspected to be CADASIL has a different novel disorder with dissimilar p

16 ngation of O-fucose on Notch3 is impaired by CADASIL mutations.

17 onal nature of the Notch 3 mutations causing CADASIL and their mechanistic connection to small-vessel

18 lay hallmarks of the ischemic stroke disease CADASIL.

19 ular macrophages were greater in the English CADASIL samples compared to those from the Swedish brain

20 skin biopsies confirmed that the patient had CADASIL.

21 may be the primary molecular abnormality in CADASIL.

22 irst cells affected by Notch3 aggregation in CADASIL mice.

23 bserved increased staining of capillaries in CADASIL for types I, IV, and VI collagen.

24 ease of types I, III, IV, and VI collagen in CADASIL brains.

25 vascular collagen subtypes are increased in CADASIL in multiple layers of all sizes of arteries, wit

26 tion in the vascular extracellular matrix in CADASIL is a key contributor to cerebrovascular dysfunct

27 llagen accumulation in the vascular media in CADASIL.

28 ct collagen subtype distribution patterns in CADASIL.

29 e for structurally altered NOTCH3 protein in CADASIL tissue.

30 ese data suggest that Fringe plays a role in CADASIL pathophysiology.

31 am of Notch3(ECD) deposition, play a role in CADASIL, producing divergent influences on early CBF def

32 ubcortical infarcts and leucoencephalopathy (CADASIL) but their genetic identities remain unknown.

33 ubcortical infarcts and leucoencephalopathy (CADASIL), an autosomal dominant cerebral arteriopathy, i

34 ubcortical infarcts and leucoencephalopathy (CADASIL), due to mutations in the NOTCH: 3 gene, is incr

35 ubcortical infarcts and leucoencephalopathy (CADASIL)and some forms of cerebral amyloid angiopathy ha

36 subcortical infarcts and leukoencephalopathy CADASIL is caused by more than a hundred NOTCH3 mutation

37 ubcortical infarcts and leukoencephalopathy (CADASIL) are susceptible to smooth muscle loss and fibro

38 ubcortical infarcts and leukoencephalopathy (CADASIL) is a genetically linked neurologic disease char

39 ubcortical infarcts and leukoencephalopathy (CADASIL) is a neurological syndrome characterized by sma

40 ubcortical infarcts and leukoencephalopathy (CADASIL) is a vascular dementia arising from abnormal ar

41 ubcortical infarcts and leukoencephalopathy (CADASIL) syndrome of premature stroke and dementia is a

42 ubcortical infarcts and leukoencephalopathy (CADASIL), caused by dominant mutations in the NOTCH3 rec

43 ubcortical infarcts and leukoencephalopathy (CADASIL), the most common inherited small-vessel disease

44 ubcortical infarcts and leukoencephalopathy (CADASIL), which is associated with mutations in the Notc

45 ubcortical infarcts and leukoencephelopathy (CADASIL) syndrome, a heritable arteriopathy predisposing

46 ve been linked to the Marfan syndrome (MFS), CADASIL, protein S deficiency, haemophilia B and familia

47 xperiments to detect epitopes in post-mortem CADASIL brains (n=8), control brains, and cells overexpr

48 conditions involving the vasculature, namely CADASIL (cerebral autosomal dominant arteriopathy with s

49 Within the thickened penetrating arteries of CADASIL patients, all four collagens extended through mo

50 d vitronectin are responsible for aspects of CADASIL disease phenotypes.

51 In a large prospectively recruited cohort of CADASIL subjects we determined relationships between phe

52 To examine the functional consequences of CADASIL mutations, we engineered 4 CADASIL-like mutation

53 , although he has a concomitant diagnosis of CADASIL (cerebral arteriopathy, autosomal dominant, with

54 1C mutation in the NOTCH3 gene diagnostic of CADASIL.

55 scular smooth muscle cells, is a hallmark of CADASIL and other SVDs, including diabetic retinopathy,

56 e exclusive cerebrovascular manifestation of CADASIL.

57 c (Tg)Notch3(R169C) mice, a genetic model of CADASIL, revealed functional defects in cerebral (pial)

58 ice, a well-established preclinical model of CADASIL.

59 cells may play a role in the pathogenesis of CADASIL.

60 ings open opportunities for the treatment of CADASIL and other SVDs by modulating Notch3 signaling.

61 Two-, 7-, and 12-month-old CADASIL mutant mice (TgNotch3(R169C) ) and wild-type con

62 In a clinically relevant CADASIL mouse model, we show that exogenous ADAM17 or HB

63 is of human brain vessels, carrying the same CADASIL mutations, identified clusterin and collagen 18

64 One hundred and twenty-seven CADASIL cases from 65 families with 17 different mutatio

65 lagen in brains obtained at autopsy from six CADASIL patients with cysteine-altering mutations in NOT

66 Mutations in Notch3 cause the syndrome CADASIL (cerebral autosomal dominant arteriopathy with s

67 l infarcts and leukoencephalopathy syndrome (CADASIL), a disorder caused by NOTCH3 gene mutations exp

68 We conclude that CADASIL arteries feature latent N-terminal NOTCH3 epitop

69 We determine that CADASIL pathophysiology is associated with hypomorphic N

70 Based upon clinical evidence that CADASIL arteriopathy results in degeneration and loss of

71 phenotype and increases the likelihood that CADASIL joins the growing list of neurological diseases

72 cluding the mutational hot spot, showed that CADASIL mutations do not affect the addition of O-fucose

73 tch paralogs and orthologs that suggest that CADASIL mutations result in a gain of function.

74 sight into how Notch 3 function is linked to CADASIL pathophysiology, we studied two phenotypically d

75 It is not known whether CADASIL mutations lead to loss or gain of Notch3 recepto

76 ulation in the English family afflicted with CADASIL.

77 troke and vascular dementia in patients with CADASIL (cerebral autosomal dominant arteriopathy with s

78 s on brain vessels of mice and patients with CADASIL.