The Role of Vascular Endothelial Growth Factor in Neurodegeneration and Cognitive Decline

Hohman, Timothy J.; Bell, Susan P.; Jefferson, Angela L.

doi:10.1001/jamaneurol.2014.4761

Cited by 147 publications

(122 citation statements)

References 39 publications

(59 reference statements)

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“…Brain protective actions of VEGF are suggested by findings in mice [34] and human subjects [16,21]. In a North American population of older people (the Alzheimer's Disease Neuroimaging Initiative, or ADNI, cohort) VEGF concentration in CSF was positively associated with better brain aging-related outcomes (hippocampal atrophy, and composite measures of episodic memory and executive function) [21].…”

Section: Discussionmentioning

confidence: 99%

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Age-dependent expression of VEGFR2 in deep brain arteries in small vessel disease, CADASIL, and healthy brains

Ahmed-Jushuf

Jiwa

Arwani

et al. 2016

Neurobiology of Aging

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Vascular myocytes are central to brain aging. Small vessel disease (SVD; arteriolosclerosis) is a widespread cause of lacunar stroke and vascular dementia, and is characterised by fibrosis and depletion of vascular myocytes in small penetrating arteries. Vascular endothelial growth factor (VEGF) is associated with brain aging, and VEGFR2 is a potent determinant of cell fate. Here, we tested whether VEGFR2 in vascular myocytes is associated with older age and SVD in human brain.VEGFR2 immunolabelling in deep grey matter was assessed in older people with or without moderate-severe SVD, or in younger people without brain pathology or with a monogenic form of SVD (CADASIL). All cases were without Alzheimer's disease pathology. Myocyte VEGFR2 was associated with increasing age (p=0.0026) but not with SVD pathology or with sclerotic index or blood vessel density. We conclude that VEGFR2 is consistently expressed in small artery myocytes of older people, and may mediate effects of VEGF on brain vascular aging.[word count: 156; <170]

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Section: Discussionmentioning

confidence: 99%

“…In a recent longitudinal study of older people, VEGF concentration in CSF was positively associated with better brain aging outcomes, including episodic memory and executive function [21].…”

Section: Introductionmentioning

confidence: 97%

Age-dependent expression of VEGFR2 in deep brain arteries in small vessel disease, CADASIL, and healthy brains

Ahmed-Jushuf

Jiwa

Arwani

et al. 2016

Neurobiology of Aging

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show abstract

“…In particular, loss of arterial elasticity is accompanied by cognitive decline (Rabkin, 2012; Unverzagt et al, 2011), can greatly increase the risk of cerebrovascular accidents (Hatanaka et al, 2011; Mattace-Raso et al, 2006), and has been linked to the accumulation of beta-amyloid in Alzheimer’s Disease (Casserly & Topol, 2004; Kalaria et al, 2012; see also Hohman et al, 2015). There is also evidence that vascular risk factors may influence brain anatomy and cognitive function even in the absence of stroke or Alzheimer’s disease.…”

Section: Introductionmentioning

confidence: 99%

“…Although the mechanisms behind these associations are not entirely clear, it is possible that arterial stiffness and/or chronic vasoconstriction may cause chronic brain hypoperfusion, which in turn can lead to brain atrophy, even at sub-clinical levels. Another possibility is that endothelial dysfunction, such as down-regulation of the endothelial growth factor, may play a role in neurodegeneration and cognitive decline (Hohman et al, 2015). …”

Section: Introductionmentioning

confidence: 99%

Individual differences in regional cortical volumes across the life span are associated with regional optical measures of arterial elasticity

et al. 2017

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Aging is often accompanied by changes in brain anatomy and cerebrovascular health. However, the specific relationship between declines in regional cortical volumes and loss of cerebral arterial elasticity is less clear, as only global or very localized estimates of cerebrovascular health have been available. Here we employed a novel tomographic optical method (pulse-DOT) to derive local estimates of cerebral arterial elasticity and compared regional volumetric estimates (obtained with FreeSurfer) with optical arterial elasticity estimates from the same regions in 47 healthy adults (aged 18–75). Between-subject analyses revealed a global correlation between cortical volume and cortical arterial elasticity, which was a significant mediator of the association between age and cortical volume. Crucially, a novel within-subject analysis highlighted the spatial association between regional variability in cortical volumes and arterial elasticity in the same regions. This association strengthened with age. Gains in the predictability of cortical volumes from arterial elasticity data were obtained by sharpening the resolution up to individual cortical regions. These results indicate that some of the variance of sub-clinical age-related brain atrophy is associated with differences in the status of cerebral arteries, and can help to explain the unique patterns of brain atrophy found within each individual.

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“…Several downstream signaling molecules are reported to trigger under hypoxia. Vascular endothelial growth factor (VEGF) is one of them, which is responsible for the formation of new blood vessels (angiogenesis) and lead to the supply of nutrients and oxygen for normal homeostasis [2]. Moreover, the crucial role of VEGF in the brain is not restricted only to controlling vessel growth: But it has direct effects on different types of neural cells including neural stem cells.…”

Section: Introductionmentioning

confidence: 99%

Biomolecules Mediated Targeting of Vascular Endothelial Growth Factor in Neuronal Dysfunction: An in Silico Approach

Jha

Kumar

2017

Asian J Pharm Clin Res

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Objective: Neurodegenerative diseases are a debilitating age-related disorder manifested by memory loss, impaired motor activity, and loss of muscle tone due to the accumulation of toxic metabolites in the brain. Despite the knowledge of factors causing neurodegenerative disorders, it remains irreversible and incurable. Growing evidence have currently advocated the physiological and pathological contribution of hypoxia-induced vascular endothelial growth factor (VEGF) in neuronal loss. The objective of this research report highlights biomolecules mediated targeting of VEGF activity based on in silico approaches that could establish a potential therapeutic window for the treatment of different abnormalities associated with impaired VEGF.Results: Three-dimensional structure of VEGF was generated and Ramachandran plot obtained for quality assessment. RAMPAGE displayed 99.5% of residues in the most favored regions, 0.5% residues in additionally allowed, and no residues in disallowed regions in VEGF, showing that stereochemical quality of protein structure is good. Further, initial screenings of the molecules were done based on Lipinski's rule of five. Finally, we have found Naringenin to be most effective among three biomolecules in modulating VEGF activity based on minimum inhibition constant, Ki, and highest negative free energy of binding with the maximum interacting surface area during docking studies. Conclusion:The present study outlines the novel potential of biomolecules in regulating VEGF activity for the treatment of different abnormalities associated with impaired VEGF.

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The Role of Vascular Endothelial Growth Factor in Neurodegeneration and Cognitive Decline

Cited by 147 publications

References 39 publications

Age-dependent expression of VEGFR2 in deep brain arteries in small vessel disease, CADASIL, and healthy brains

Age-dependent expression of VEGFR2 in deep brain arteries in small vessel disease, CADASIL, and healthy brains

Individual differences in regional cortical volumes across the life span are associated with regional optical measures of arterial elasticity

Biomolecules Mediated Targeting of Vascular Endothelial Growth Factor in Neuronal Dysfunction: An in Silico Approach

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