Cerebrovascular disorders associated with genetic lesions

Karschnia, Philipp; Nishimura, Sadako; Louvi, Angeliki

doi:10.1007/s00018-018-2934-5

Cited by 17 publications

(15 citation statements)

References 243 publications

(242 reference statements)

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“…Notch pathway dysfunction has been unequivocally linked to ischemic stroke by virtue of the fact that NOTCH3 mutations underlie CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) (Chabriat, Joutel, Dichgans, Tournier-Lasserve, & Bousser, 2009;Joutel et al, 1996;Karschnia, Nishimura, & Louvi, 2019;Louvi & Artavanis-Tsakonas, 2012). CADASIL is the most common monogenic (hereditary) form of ischemic stroke leading to cognitive decline and dementia.…”

Section: Notch In Ischemia and Brain Injurymentioning

confidence: 99%

The Notch pathway in CNS homeostasis and neurodegeneration

Artavanis‐Tsakonas

Louvi

2019

WIREs Developmental Biology

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The role of the Notch signaling pathway in neural development has been well established over many years. More recent studies, however, have demonstrated that Notch continues to be expressed and active throughout adulthood in many areas of the central nervous system. Notch signals have been implicated in adult neurogenesis, memory formation, and synaptic plasticity in the adult organism, as well as linked to acute brain trauma and chronic neurodegenerative conditions. NOTCH3 mutations are responsible for the most common form of hereditary stroke, the progressive disorder cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Notch has also been associated with several progressive neurodegenerative diseases, including Alzheimer's disease, multiple sclerosis, and amyotrophic lateral sclerosis. Although numerous studies link Notch activity with CNS homeostasis and neurodegenerative diseases, the data thus far are primarily correlative, rather than functional. Nevertheless, the evidence for Notch pathway activity in specific neural cellular contexts is strong, and certainly intriguing, and points to the possibility that the pathway carries therapeutic promise. This article is categorized under: Nervous System Development > Flies Signaling Pathways > Cell Fate Signaling Nervous System Development > Vertebrates: General Principles

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Section: Notch In Ischemia and Brain Injurymentioning

confidence: 99%

The Notch pathway in CNS homeostasis and neurodegeneration

Artavanis‐Tsakonas

Louvi

2019

WIREs Developmental Biology

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“…Several human genetic diseases affecting the cerebral vasculature are linked to the Notch pathway. For example, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic form of ischaemic stroke and is caused by mutations in the Notch receptor NOTCH . Cerebral cavernous malformations (CCMs) are common large vascular cavernomas due to enlarged brain sinusoids.…”

Section: Discussionmentioning

confidence: 99%

Cerebrovascular endothelial cells form transient Notch‐dependent cystic structures in zebrafish

Kugler

Lessen²,

Daetwyler

et al. 2019

EMBO Reports

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We identify a novel endothelial membrane behaviour in transgenic zebrafish. Cerebral blood vessels extrude large transient spherical structures that persist for an average of 23 min before regressing into the parent vessel. We term these structures “kugeln”, after the German for sphere. Kugeln are only observed arising from the cerebral vessels and are present as late as 28 days post fertilization. Kugeln do not communicate with the vessel lumen and can form in the absence of blood flow. They contain little or no cytoplasm, but the majority are highly positive for nitric oxide reactivity. Kugeln do not interact with brain lymphatic endothelial cells (BLECs) and can form in their absence, nor do they perform a scavenging role or interact with macrophages. Inhibition of actin polymerization, Myosin II, or Notch signalling reduces kugel formation, while inhibition of VEGF or Wnt dysregulation (either inhibition or activation) increases kugel formation. Kugeln represent a novel Notch‐dependent NO‐containing endothelial organelle restricted to the cerebral vessels, of currently unknown function.

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“…Because of the focus of this review, we will not describe the genetic factors associated with cerebrovascular disease other than CAA. An overview of the current knowledge of select cerebrovascular disorders that are associated with genetic lesions is provided elsewhere (Karschnia, Nishimura, & Louvi, 2019).…”

Section: Genetic Factors Associated With Caamentioning

confidence: 99%

Down syndrome, Alzheimer disease, and cerebral amyloid angiopathy: The complex triangle of brain amyloidosis

Carmona-Iragui

Videla

Lleó

et al. 2019

Developmental Neurobiology

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Down syndrome (DS) is the main genetic cause of intellectual disability worldwide. The overexpression of the Amyloid Precursor Protein, present in chromosome 21, leads to β‐amyloid deposition that results in Alzheimer disease (AD) and, in most cases, also to cerebral amyloid angiopathy (CAA) neuropathology. People with DS invariably develop the neuropathological hallmarks of AD at the age of 40, and they are at an ultra high risk for suffering AD‐related cognitive impairment thereafter. In the general population, cerebrovascular disease is a significant contributor to AD‐related cognitive impairment, while in DS remains understudied. This review describes the current knowledge on cerebrovascular disease in DS and reviews the potential biomarkers that could be useful in the future studies, focusing on CAA. We also discuss available evidence on sporadic AD or other genetically determined forms of AD. We highlight the urgent need of large biomarker‐characterized cohorts, including neuropathological correlations, to study the exact contribution of CAA and related vascular factors that play a role in cognition and occur with aging, their characterization and interrelationships. DS represents a unique context in which to perform these studies as this population is relatively protected from some conventional vascular risk factors and they develop significant CAA, DS represents a particular atheroma‐free model to study AD‐related vascular pathologies. Only deepening on these underlying mechanisms, new preventive and therapeutic strategies could be designed to improve the quality of life of this population and their caregivers and lead to new avenues of treatment also in the general AD population.

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Cerebrovascular disorders associated with genetic lesions

Cited by 17 publications

References 243 publications

The Notch pathway in CNS homeostasis and neurodegeneration

The Notch pathway in CNS homeostasis and neurodegeneration

Cerebrovascular endothelial cells form transient Notch‐dependent cystic structures in zebrafish

Down syndrome, Alzheimer disease, and cerebral amyloid angiopathy: The complex triangle of brain amyloidosis

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