Tau Protein and Its Role in Blood–Brain Barrier Dysfunction

Michalicová, Alena; Majerová, Petra; Kováč, Andrej

doi:10.3389/fnmol.2020.570045

Cited by 89 publications

(75 citation statements)

References 152 publications

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“…Interestingly, at the opposite end of the aging spectrum, defects in the integrity of the NVU of the BBB are considered to underly neurodegenerative disease ( 72 ) and may be linked to conditions such as diabetes ( 73 ). Similar defects in the BRB are linked to age-related disease in the eye which have an underlying inflammatory pathogenesis ( 74 , 75 ).…”

Section: Immune Defense Immune Privilege and Tissue Barriers: Intermentioning

confidence: 99%

Immune Privilege: The Microbiome and Uveitis

et al. 2021

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Immune privilege (IP), a term introduced to explain the unpredicted acceptance of allogeneic grafts by the eye and the brain, is considered a unique property of these tissues. However, immune responses are modified by the tissue in which they occur, most of which possess IP to some degree. The eye therefore displays a spectrum of IP because it comprises several tissues. IP as originally conceived can only apply to the retina as it contains few tissue-resident bone-marrow derived myeloid cells and is immunologically shielded by a sophisticated barrier – an inner vascular and an outer epithelial barrier at the retinal pigment epithelium. The vascular barrier comprises the vascular endothelium and the glia limitans. Immune cells do not cross the blood-retinal barrier (BRB) despite two-way transport of interstitial fluid, governed by tissue oncotic pressure. The BRB, and the blood-brain barrier (BBB) mature in the neonatal period under signals from the expanding microbiome and by 18 months are fully established. However, the adult eye is susceptible to intraocular inflammation (uveitis; frequency ~200/100,000 population). Uveitis involving the retinal parenchyma (posterior uveitis, PU) breaches IP, while IP is essentially irrelevant in inflammation involving the ocular chambers, uveal tract and ocular coats (anterior/intermediate uveitis/sclerouveitis, AU). Infections cause ~50% cases of AU and PU but infection may also underlie the pathogenesis of immune-mediated “non-infectious” uveitis. Dysbiosis accompanies the commonest form, HLA-B27–associated AU, while latent infections underlie BRB breakdown in PU. This review considers the pathogenesis of uveitis in the context of IP, infection, environment, and the microbiome.

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Section: Immune Defense Immune Privilege and Tissue Barriers: Intermentioning

confidence: 99%

Immune Privilege: The Microbiome and Uveitis

et al. 2021

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“…Upregulation of senescence was inferred by elevated expression of Serpine1 , Cxcl8 , Cxcl1 , Cxcl2 , Csf2 , and Cdkn1a ; however, other markers of senescence were not evaluated [ 167 ]. Whether tauopathy causes endothelial senescence and induces a leaky BBB and/or endothelial senescence affects the vascular microenvironment will require further investigation [ 168 ].…”

Section: Endothelial Cellsmentioning

confidence: 99%

The Cellular Senescence Stress Response in Post-Mitotic Brain Cells: Cell Survival at the Expense of Tissue Degeneration

Sah

Krishnamurthy

Ahmidouch

et al. 2021

Life

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In 1960, Rita Levi-Montalcini and Barbara Booker made an observation that transformed neuroscience: as neurons mature, they become apoptosis resistant. The following year Leonard Hayflick and Paul Moorhead described a stable replicative arrest of cells in vitro, termed “senescence”. For nearly 60 years, the cell biology fields of neuroscience and senescence ran in parallel, each separately defining phenotypes and uncovering molecular mediators to explain the 1960s observations of their founding mothers and fathers, respectively. During this time neuroscientists have consistently observed the remarkable ability of neurons to survive. Despite residing in environments of chronic inflammation and degeneration, as occurs in numerous neurodegenerative diseases, often times the neurons with highest levels of pathology resist death. Similarly, cellular senescence (hereon referred to simply as “senescence”) now is recognized as a complex stress response that culminates with a change in cell fate. Instead of reacting to cellular/DNA damage by proliferation or apoptosis, senescent cells survive in a stable cell cycle arrest. Senescent cells simultaneously contribute to chronic tissue degeneration by secreting deleterious molecules that negatively impact surrounding cells. These fields have finally collided. Neuroscientists have begun applying concepts of senescence to the brain, including post-mitotic cells. This initially presented conceptual challenges to senescence cell biologists. Nonetheless, efforts to understand senescence in the context of brain aging and neurodegenerative disease and injury emerged and are advancing the field. The present review uses pre-defined criteria to evaluate evidence for post-mitotic brain cell senescence. A closer interaction between neuro and senescent cell biologists has potential to advance both disciplines and explain fundamental questions that have plagued their fields for decades.

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“…The proper function of BBB requires cooperation between endothelium, astrocytes, neurons, and extracellular matrix. An important role in a progression of neurological diseases is a disruption of the BBB integrity [ 168 , 169 ]. Degeneration of BBB has been confirmed in different disease—AD, PD, ALS, multiple sclerosis (MS), vascular dementia, stroke, hypoxia, or ischemia [ 170 ].…”

Section: The Sarco/endoplasmic Reticulum Ca 2+mentioning

confidence: 99%

Crosstalk among Calcium ATPases: PMCA, SERCA and SPCA in Mental Diseases

Boczek

Sobolczyk

Mackiewicz

et al. 2021

IJMS

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Calcium in mammalian neurons is essential for developmental processes, neurotransmitter release, apoptosis, and signal transduction. Incorrectly processed Ca2+ signal is well-known to trigger a cascade of events leading to altered response to variety of stimuli and persistent accumulation of pathological changes at the molecular level. To counterbalance potentially detrimental consequences of Ca2+, neurons are equipped with sophisticated mechanisms that function to keep its concentration in a tightly regulated range. Calcium pumps belonging to the P-type family of ATPases: plasma membrane Ca2+-ATPase (PMCA), sarco/endoplasmic Ca2+-ATPase (SERCA) and secretory pathway Ca2+-ATPase (SPCA) are considered efficient line of defense against abnormal Ca2+ rises. However, their role is not limited only to Ca2+ transport, as they present tissue-specific functionality and unique sensitive to the regulation by the main calcium signal decoding protein—calmodulin (CaM). Based on the available literature, in this review we analyze the contribution of these three types of Ca2+-ATPases to neuropathology, with a special emphasis on mental diseases.

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Tau Protein and Its Role in Blood–Brain Barrier Dysfunction

Cited by 89 publications

References 152 publications

Immune Privilege: The Microbiome and Uveitis

Immune Privilege: The Microbiome and Uveitis

The Cellular Senescence Stress Response in Post-Mitotic Brain Cells: Cell Survival at the Expense of Tissue Degeneration

Crosstalk among Calcium ATPases: PMCA, SERCA and SPCA in Mental Diseases

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