Abstract
The blood-brain barrier (BBB) and the blood-spinal cord barrier (BSCB) are responsible for controlling the microenvironment within neural tissues in humans. These barriers are fundamental to all neurological processes as they provide the extreme nutritional demands of neural tissue, remove wastes, and maintain immune privileged status. Being a semipermeable membrane, both the BBB and BSCB allow the diffusion of certain molecules, whilst restricting others. In amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases, these barriers become hyperpermeable, allowing a wider variety of molecules to pass through leading to more severe and more rapidly progressing disease. The intention of this review is to discuss evidence that BBB hyperpermeability is potentially a disease driving feature in ALS and other neurodegenerative diseases. The various biochemical, physiological, and genomic factors that can influence BBB permeability in ALS and other neurodegenerative diseases are also discussed, in addition to novel therapeutic strategies centred upon the BBB.
Highlights
The blood-brain barrier (BBB) is a highly selective, semipermeable complex that surrounds most of the blood vessels in the brain [1], except for the circumventricular organs (CVOs) centred around the ventricles of the brain
With a panel of miRNAs identified to have differential expression induced by inflammatory mediators that displayed opposing changes after barrier induction in the cell line, the authors further examined their expression in brain capillaries isolated via filtration from resected multiple sclerosis patient lesions. These samples showed decreased expression of miR-125a-5p [155]. miR125a-5p is a key regulator of brain endothelial tightness and immune cell efflux, and these findings suggest that repair of a disturbed BBB through microRNAs may represent a novel avenue for effective treatment of MS and can be applied to other neurodegenerative diseases
This review aimed to provide insight into the physiological, biochemical, and novel genomic mechanisms behind BBB
Summary
The blood-brain barrier (BBB) is a highly selective, semipermeable complex that surrounds most of the blood vessels in the brain [1], except for the circumventricular organs (CVOs) centred around the ventricles of the brain. There is reason to believe that the permeability of the BBB and BSCB differs with evidence suggesting that the BSCB is more permeable [5] This difference in permeability has attracted motor neuron disease (MND) research, with findings suggesting that the BSCB is damaged in human and rodent ALS sufferers. Despite this evidence, the BSCB (like the BBB) breakdown in disease pathogenesis remains unclear [6, 7]. Adherence junctions (AJs) are more basal than TJs and are defined by their cytoplasmic face being linked to the actin cytoskeleton [8] It is currently accepted in scientific literature that all the components of the BBB are essential for normal function and stability of the BBB. This review will make recommendations to investigative areas that hold promise in understanding the mechanisms involved in BBB breakdown at the biological and molecular level and provide insights into therapeutic strategies to modulate BBB permeability
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