The “Frail” Brain Blood Barrier in Neurodegenerative Diseases: Role of Early Disruption of Endothelial Cell-to-Cell Connections

Maiuolo, Jessica; Gliozzi, Micaela; Musolino, Vincenzo; Scicchitano, Miriam; Carresi, Cristina; Scarano, Federica; Bosco, Francesca; Nucera, Saverio; Ruga, Stefano; Zito, Maria Caterina; Mollace, Vincenzo; Palma, Ernesto; Fini, Massimo; Muscoli, Carolina; Mollace, Vincenzo

doi:10.3390/ijms19092693

Cited by 68 publications

(64 citation statements)

References 131 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The close association of CECs and neural cells allows the signals by CEC damage to be transduced to the brain [e.g., the impaired NO function alters the synaptic plasticity ( Blackshaw et al, 2003 )]. Therefore, signal disturbances of NVU might underlie the nerve injury, apoptosis and neurological dysfunction ( Lourenco et al, 2018 ; Maiuolo et al, 2018 ). Thus, CECs are not only the primary components of BBB structurally but also the key link of NVU activities functionally.…”

Section: Structural and Functional Characteristics Of Cecsmentioning

confidence: 99%

Dysfunction of Cerebrovascular Endothelial Cells: Prelude to Vascular Dementia

Wang

Cao

et al. 2018

Front. Aging Neurosci.

122

108

View full text Add to dashboard Cite

Vascular dementia (VaD) is the second most common type of dementia after Alzheimer’s disease (AD), characterized by progressive cognitive impairment, memory loss, and thinking or speech problems. VaD is usually caused by cerebrovascular disease, during which, cerebrovascular endothelial cells (CECs) are vulnerable. CEC dysfunction occurs before the onset of VaD and can eventually lead to dysregulation of cerebral blood flow and blood–brain barrier damage, followed by the activation of glia and inflammatory environment in the brain. White matter, neuronal axons, and synapses are compromised in this process, leading to cognitive impairment. The present review summarizes the mechanisms underlying CEC impairment during hypoperfusion and pathological role of CECs in VaD. Through the comprehensive examination and summarization, endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) signaling pathway, Ras homolog gene family member A (RhoA) signaling pathway, and CEC-derived caveolin-1 (CAV-1) are proposed to serve as targets of new drugs for the treatment of VaD.

show abstract

Section: Structural and Functional Characteristics Of Cecsmentioning

confidence: 99%

Dysfunction of Cerebrovascular Endothelial Cells: Prelude to Vascular Dementia

Wang

Cao

et al. 2018

Front. Aging Neurosci.

122

108

View full text Add to dashboard Cite

show abstract

“…The blood-brain barrier (BBB) neuro vascular unit (NVU), made up of neurons, astrocytes, pericytes, microglia and endothelial cells, can counteract the effects of oxidation when the amount of ROS is limited and when the activity of antioxidant enzymes is preserved. Any imbalance in the NVU functioning may alter the brain homeostasis, resulting in high oxidative stress and the impairment of the integrity of the BBB [14,15].…”

Section: Oxidative Metabolism In Neurodegenerative Diseasesmentioning

confidence: 99%

“…Co-Q10 is able to inhibit the release of pro-inflammatory cytokines (IL-6, IL8 and TNF-α) by the endothelial cells as well as to reduce the expression of those proteins (integrins, selectins, ICAM, VCAM) capable of putting the endothelium in contact with the blood monocytes. The reduced expression of these proteins minimises the passage of the immune cells through the BBB [15,37]. Co-Q10 can also reduce the stress of the endoplasmic reticulum organelle, which underlies the main neurodegenerative diseases due to a strong "protein folding" process, the altered communication with the mitochondrion organelles-resulting in oxidative stress-as well as to changes in the concentration of the calcium ion.…”

Section: Coenzyme Q10mentioning

confidence: 99%

The Potential for Natural Antioxidant Supplementation in the Early Stages of Neurodegenerative Disorders

Oppedisano

Maiuolo

Gliozzi

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

The neurodegenerative process is characterized by the progressive ultrastructural alterations of selected classes of neurons accompanied by imbalanced cellular homeostasis, a process which culminates, in the later stages, in cell death and the loss of specific neurological functions. Apart from the neuronal cell impairment in selected areas of the central nervous system which characterizes many neurodegenerative diseases (e.g., Alzheimer’s Disease, Parkinson’s Disease, Huntington’s Disease, etc.), some alterations may be found in the early stages including gliosis and the misfolding or unfolding accumulation of proteins. On the other hand, several common pathophysiological mechanisms can be found early in the course of the disease including altered oxidative metabolism, the loss of cross-talk among the cellular organelles and increased neuroinflammation. Thus, antioxidant compounds have been suggested, in recent years, as a potential strategy for preventing or counteracting neuronal cell death and nutraceutical supplementation has been studied in approaching the early phases of neurodegenerative diseases. The present review will deal with the pathophysiological mechanisms underlying the early stages of the neurodegenerative process. In addition, the potential of nutraceutical supplementation in counteracting these diseases will be assessed.

show abstract

“…This system of barriers is particularly important both in the Central Nervous System (CNS) and in the peripheral nerve. However, although the blood-brain barrier (BBB) has been extensively studied in its implications in the development of neurodegenerative diseases [1], the mechanisms that regulate exchanges between blood and peripheral nerve, the so-called Blood Nerve Barrier (BNB), has been less studied, especially in its implications with peripheral neuropathies.…”

Section: Introductionmentioning

confidence: 99%

The Role of Endothelial Dysfunction in Peripheral Blood Nerve Barrier: Molecular Mechanisms and Pathophysiological Implications

Maiuolo

Gliozzi

Musolino

et al. 2019

IJMS

Self Cite

View full text Add to dashboard Cite

The exchange of solutes between the blood and the nerve tissue is mediated by specific and high selective barriers in order to ensure the integrity of the different compartments of the nervous system. At peripheral level, this function is maintained by the Blood Nerve Barrier (BNB) that, in the presence, of specific stressor stimuli can be damaged causing the onset of neurodegenerative processes. An essential component of BNB is represented by the endothelial cells surrounding the sub-structures of peripheral nerves and increasing evidence suggests that endothelial dysfunction can be considered a leading cause of the nerve degeneration. The purpose of this review is to highlight the main mechanisms involved in the impairment of endothelial cells in specific diseases associated with peripheral nerve damage, such as diabetic neuropathy, erectile dysfunction and inflammation of the sciatic nerve.

show abstract

The “Frail” Brain Blood Barrier in Neurodegenerative Diseases: Role of Early Disruption of Endothelial Cell-to-Cell Connections

Cited by 68 publications

References 131 publications

Dysfunction of Cerebrovascular Endothelial Cells: Prelude to Vascular Dementia

Dysfunction of Cerebrovascular Endothelial Cells: Prelude to Vascular Dementia

The Potential for Natural Antioxidant Supplementation in the Early Stages of Neurodegenerative Disorders

The Role of Endothelial Dysfunction in Peripheral Blood Nerve Barrier: Molecular Mechanisms and Pathophysiological Implications

Contact Info

Product

Resources

About