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The Blood–Brain Barrier and Its Intercellular Junctions in Age-Related Brain Disorders

1
Institute of Life Sciences, Vasile Goldiş Western University of Arad, 310414 Arad, Romania
2
Institute of Biophysics, Biological Research Centre, 6726 Szeged, Hungary
3
Doctoral School of Biology, University of Szeged, 6726 Szeged, Hungary
4
Department of Biological Sciences, University of Salzburg, 5020 Salzburg, Austria
5
Institute of Tendon and Bone Regeneration, Paracelsus Medical University—Spinal Cord Injury and Tissue Regeneration Center Salzburg, 5020 Salzburg, Austria
6
Department of Physiology, Anatomy and Neuroscience, University of Szeged, 6726 Szeged, Hungary
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this study.
Int. J. Mol. Sci. 2019, 20(21), 5472; https://doi.org/10.3390/ijms20215472
Received: 12 October 2019 / Revised: 30 October 2019 / Accepted: 1 November 2019 / Published: 3 November 2019
(This article belongs to the Special Issue The Tight Junction and Its Proteins: More Than Just a Barrier)
With age, our cognitive skills and abilities decline. Maybe starting as an annoyance, this decline can become a major impediment to normal daily life. Recent research shows that the neurodegenerative disorders responsible for age associated cognitive dysfunction are mechanistically linked to the state of the microvasculature in the brain. When the microvasculature does not function properly, ischemia, hypoxia, oxidative stress and related pathologic processes ensue, further damaging vascular and neural function. One of the most important and specialized functions of the brain microvasculature is the blood–brain barrier (BBB), which controls the movement of molecules between blood circulation and the brain parenchyma. In this review, we are focusing on tight junctions (TJs), the multiprotein complexes that play an important role in establishing and maintaining barrier function. After a short introduction of the cell types that modulate barrier function via intercellular communication, we examine how age, age related pathologies and the aging of the immune system affects TJs. Then, we review how the TJs are affected in age associated neurodegenerative disorders: Alzheimer’s disease and Parkinson’s disease. Lastly, we summarize the TJ aspects of Huntington’s disease and schizophrenia. Barrier dysfunction appears to be a common denominator in neurological disorders, warranting detailed research into the molecular mechanisms behind it. Learning the commonalities and differences in the pathomechanism of the BBB injury in different neurological disorders will predictably lead to development of new therapeutics that improve our life as we age. View Full-Text
Keywords: aging; blood–brain barrier; tight junction aging; blood–brain barrier; tight junction
MDPI and ACS Style

Costea, L.; Mészáros, Á.; Bauer, H.; Bauer, H.-C.; Traweger, A.; Wilhelm, I.; Farkas, A.E.; Krizbai, I.A. The Blood–Brain Barrier and Its Intercellular Junctions in Age-Related Brain Disorders. Int. J. Mol. Sci. 2019, 20, 5472.

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