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Disruption of blood-brain barrier in amyotrophic lateral sclerosis: an update

  • Clinical Neurochemistry
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Abstract

Amyotrophic lateral sclerosis (ALS) is a continuously progressing neurodegenerative disease that is characterized by selective damage to motoneurons in the neocortex, brainstem, and spinal cord. The general opinion is that sporadic ALS is a multifactor and multigene disease. Realization of its genetic predisposition is determined by environmental factors. The blood-brain barrier (BBB) is the border for the neurons of the brain and spinal cord, where they interact with environmental factors. Current knowledge on BBB alterations during ALS helps to reevaluate views on the pathogenesis of the disease, as well as on the development of therapeutic means and methods of their delivery. It has been found that in ALS all BBB components, which separate CNS neurons from endogenous and exogenous damaging factors and participate in the communication between cells of nerve and immune systems, are involved in the pathological process. Currently, there are no data that show that BBB disruption triggers the death of neurons; however, it is an important mechanism of ALS pathogenesis. This should be considered during studies of this disease and development of new methods of treatment. Keeping in mind alterations of the BBB, it is possible to consider CNS cells, BBB cells, and peripheral immune cells as targets of new drugs for ALS treatment.

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Abbreviations

ROS:

reactive oxygen species

ALS:

amyotrophic lateral sclerosis

BBB:

blood-brain barrier or blood-spinal cord barrier

MMP:

matrix metalloproteinases

TIMP:

tissue inhibitors of MMP

TNF-α:

tumor necrosis factor α

ECs:

endothelial cells

JAM:

junction adhesion molecules

SOD1:

cytosolic superoxide dismutase

VEGF:

vascular endothelium growth factor

ZO:

zonula occludens

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Authors and Affiliations

  1. Research Center of Neurology, Russian Academy of Medical Sciences, Moscow, Russia

    L. V. Brylev, M. N. Zakharova & I. A. Zavalishin

  2. Laboratory of the Functional Biochemistry of the Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow, Russia

    L. V. Brylev & N. V. Gulyaeva

  3. Volokolamskoe sh. 80, Moscow, 125367, Russia

    L. V. Brylev

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  1. L. V. Brylev
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  2. M. N. Zakharova
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  3. I. A. Zavalishin
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  4. N. V. Gulyaeva
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Original Russian Text © L.V. Brylev, M.N. Zakharova, I.A. Zavalishin, N.V. Gulyaeva, 2012, published in Neirokhimiya, 2012, Vol. 29, No. 1, pp. 75–82.

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Brylev, L.V., Zakharova, M.N., Zavalishin, I.A. et al. Disruption of blood-brain barrier in amyotrophic lateral sclerosis: an update. Neurochem. J. 6, 64–70 (2012). https://doi.org/10.1134/S1819712411040064

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