In neurodegenerative diseases such as Alzheimer's and Parkinson's, neurons are gradually damaged and die, resulting in neurodegeneration. Neurodegeneration occurs not only in adults but also in infants and even embryonic stages in some cases. Characterized by the loss of large numbers of specific neurons, neurodegenerative disease is a complex disease of progressive development, severe disability, and death. It can be divided into two categories: acute and chronic. The former mainly includes stroke brain injury, and the latter mainly includes amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and Parkinson's disease (PD). Endotoxins are now recognized as a non-genetic cause of neurodegeneration on the basis of a large amount of evidence. Endotoxin levels in the blood of patients vary widely from normal levels and are associated with neurodegenerative diseases. Studies have shown that injecting endotoxin into laboratory animals can lead to neurodegeneration. Therefore, endotoxin detection can play an important role in clinical practice as a predictive tool for neurodegeneration.
Fig. 1 Senescence-mediated neurodegeneration. (Castillo X, et al., 2019)
Endotoxin is a component in the cell wall of Gram-negative bacteria, also known as lipopolysaccharide (LPS), which is a complex composed of polysaccharides, lipids, and proteins. And only when the bacteria die and dissolve or the bacterial cells are destroyed by artificial methods, the endotoxin can be released. Research has confirmed that the increase in endotoxin is related to neurodegeneration and can cause neurodegenerative diseases to a certain extent. Alzheimer's disease (AD) is a typical neurodegenerative disease. The average level of endotoxin in the blood and brain of AD patients increases two to three times more than normal, and endotoxin is also found in AD amyloid plaques. Endotoxins can drive amyloid-β production and aggregation and TAU hyperphosphorylation, leading to neuroinflammation and neurodegeneration. A single intraperitoneal injection of endotoxin to animals leads to acute hyperactivity of small and medium-sized cells, and multiple doses of endotoxin induce neurodegeneration, which has been used as a model of Parkinson's disease or AD. It is possible to determine whether human neurodegeneration is induced by measuring endotoxin levels in the blood.
Endotoxins make up most of the outer membrane of Gram-negative bacteria. The levels of endotoxin in plasma are markedly elevated during inflammatory and neurodegenerative diseases. In addition, endotoxin can directly or indirectly activate microglia and damage neurons through various cytokines, thereby causing damage to nerves. Several studies have demonstrated that the key to the detection of plasma endotoxin in neurodegeneration lies in determining if plasma endotoxin levels correlate with neurodegeneration and/or precede neurodegeneration, and whether lower plasma endotoxin levels can prevent neurodegeneration in the future. Longitudinal monitoring of disease time course will be enabled by larger studies of blood endotoxin levels in various neurodegenerative diseases. Furthermore, it's relatively easy and cheap to detect endotoxins in blood, which makes it a useful tool in clinical practice.
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