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

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 gen eral opinion is that sporadic ALS is a multifactor and multigene disease. Realization of its genetic predispo sition 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 develop ment 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 com munication 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.

Circulating nucleic acids in the plasma and serum as potential biomarkers in neurological disorders

“…The blood-brain barrier (BBB) is a semipermeable membranous barrier located at the interface between the blood and brain tissue. It is responsible for maintaining the central nervous system (CNS) homeostasis, protecting the CNS against toxic insults and pathogens, providing nutrients to the brain, and regulating the peripheral communication with the CNS ( 14 ). Under normal physiological conditions, small CNA fragments can cross the BBB and reach the circulating plasma and serum ( 3 , 5 ).…”

“…Under normal physiological conditions, small CNA fragments can cross the BBB and reach the circulating plasma and serum ( 3 , 5 ). However, pathological conditions may cause BBB disruption, an event that increases its permeability and allows the open flow of molecules, cells, and CNAs between the CNS and the peripheral circulation ( 5 , 8 , 14 ). Moreover, CNAs can be transported through the BBB in a more controlled manner, such as in cell-to-cell spread within extracellular vesicles (EVs) ( 15 ).…”

“…Moreover, CNAs can be transported through the BBB in a more controlled manner, such as in cell-to-cell spread within extracellular vesicles (EVs) ( 15 ). BBB disruption plays an important role in inflammation and cellular damage in many neurological disorders ( 3 , 8 , 14 ). The identification and quantification of CNAs can reflect pathological processes that occur in the CNS.…”

“…The most effective methods would non-invasively probe the CNS ( 3 , 9 ). The discovery that CNAs are released into the peripheral circulation and may reflect the biological mechanisms that underlie many neurological disorders has made it possible to investigate their use in the diagnosis, prognosis, and treatment monitoring in different neurological disorders ( 3 , 8 , 14 , 15 , 45 ). Many studies have already demonstrated the use of CNAs in the plasma and serum in neurological disorders, as summarized in Supplementary Table S1 and discussed in more detail below.…”

“…Furthermore, differential methylation of the RHBDF gene in plasma cfDNA of amyotrophic lateral sclerosis patients was found compared with healthy volunteers ( 83 ). Although cfDNA from plasma and serum has not been widely studied in amyotrophic lateral sclerosis, it has great potential because this disease causes cell death and damage to the BBB ( 14 ).…”