What enzymes can't cross the Blood Brain Barrier that are vital for humans to have in order to not get a disease?
For example, in Hurler's syndrome iduronidase (IDUA) enzyme doesn't cross the BBB.
Can someone tell me any lack of enzyme in the BBB that causes a disease?
To identify enzymes that cannot cross the Blood Brain Barrier (BBB) and are essential for human health, the first step is to understand the physiological role of enzymes and the function of the BBB. Enzymes are proteins responsible for catalyzing various biochemical reactions in the body, while the BBB is a highly selective barrier that separates the circulating blood from the brain tissue.
The BBB is composed of tight junctions between the endothelial cells that line the blood vessels in the brain, which restrict the passage of certain substances, including most large molecules such as proteins and enzymes. Consequently, the BBB serves to protect the brain from potentially harmful agents while maintaining optimal brain functioning.
However, in certain diseases, the lack of specific enzymes in the brain can lead to pathological conditions. One example is Gaucher's disease, a lysosomal storage disorder caused by a deficiency of the enzyme glucocerebrosidase (GBA). This enzyme normally breaks down a fatty substance called glucocerebroside in lysosomes. Due to the lack of GBA activity in the brain, the accumulation of glucocerebroside leads to neurodegenerative symptoms characteristic of Gaucher's disease.
Another example is Tay-Sachs disease, a rare inherited disorder caused by a deficiency of the enzyme hexosaminidase A (Hex A). Hex A is responsible for the breakdown of a fatty substance called GM2 ganglioside in lysosomes. Without sufficient Hex A activity, GM2 ganglioside accumulates in cells, affecting the functioning of nerve cells and resulting in progressive neurodegeneration.
In both Gaucher's disease and Tay-Sachs disease, the enzymes (GBA and Hex A, respectively) are unable to cross the BBB in sufficient quantities to prevent the accumulation of harmful substances, leading to the manifestation of these diseases.
It's worth noting that not all enzyme deficiencies that cause diseases are related to the BBB barrier permeability. Some enzyme deficiencies may result from genetic mutations that affect the production or function of the enzyme itself, rather than its ability to cross the BBB. Thus, identifying diseases solely based on whether an enzyme can cross the BBB might not provide a comprehensive understanding of the underlying mechanisms.