Pathomechanisms of Blood-Brain Barrier Disruption in ALS

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.

Figure 1

GTEx Analysis Release V7 Gene expression showing gene expressions of the SOD family of enzymes in TPM (Transcripts Per Million) represented logarithmically. SOD1 has high expression in regions of the brain, SOD 2 is uniform amongst somatic cells, and SOD3 has high expression in Aorta, Tibial, and Coronary arteries.

Figure 2

GTEx Analysis Release V7 Gene expression showing gene expressions of CAT in TPM (Transcripts Per Million) represented logarithmically.