Mechanisms underlying inflammation in neurodegeneration

ALS is characterized by progressive degeneration of upper and lower motor neurons in brain and spinal cord; average life expectancy 2-5 years after diagnosis; progression rapid.

“ALS, first described by Charcot in 1869, is a neurodegenerative disease characterized by the progressive degeneration of upper and lower motor neurons in the brain and spinal cord. ALS is always fatal, with an average life expectancy of 2–5 years after diagnosis.77”

Chronic neuroinflammation plays a major role in neurodegeneration that occurs in aging and in a broad range of diseases including Alzheimer's disease, Parkinson's disease, MS, ALS, stroke, TBI, and psychiatric diseases.

“Accumulating evidence suggests a major role of chronic neuroinflammation in the neurodegeneration that occurs in aging and in a broad range of diseases including Alzheimer's disease, Parkinson's disease, MS, ALS, stroke, TBI, and psychiatric diseases (Amor et al., 2010;Glass et al., 2010;Vikhreva et al., 2016).”

Inflammation is a hallmark of several neurodegenerative disorders, including FAP.

“Inflammation is a hallmark of several neurodegenerative disorders, including FAP70.”

Neuroinflammation is an effective endogenous defense that protects the central nervous system and aims to eliminate threats and restore homeostasis.

“Neuroinflammation is an effective endogenous defense that protects the central nervous system (CNS) and aims not only to eliminate threats but also restore homeostasis [69],”

In neurodegenerative diseases, neuroinflammation constitutes a fundamental process in which microglial cells play a key role.

“In neurodegenerative diseases, neuroinflammation constitutes a fundamental process in which microglial cells play a key role (Glass et al., 2010).”

Factors released after microglia activation contribute to stimulation of astrocytes, whose activation amplifies pro-inflammatory signals.

“These factors contribute to the stimulation of astrocytes, whose activation amplifies the pro-inflammatory signals [22].”

Microglia can bind Aβ plaques via Toll-like receptors or receptors for advanced glycation end products, promoting microglia activation and greater secretion of pro-inflammatory cytokines, chemokines, and reactive oxygen species.

“microglia can bind Aβ plaques via Toll-like receptors (TLRs) or receptors for advanced glycation end products (RAGE), both expressed on the cell surface. This process promotes microglia activation, which in turn causes a greater secretion of pro-inflammatory cytokines, chemokines, and ROS, as well.”

Increased intestinal permeability and translocation of bacteria and inflammatory bacterial products such as lipopolysaccharide might lead to inflammation and oxidative stress in the gastrointestinal tract and thereby initiate alpha-synuclein accumulation in the enteric nervous system.

“The increased intestinal permeability and the translocation of bacteria and inflammatory bacterial products (e.g., lipopolysaccharide, LPS) might lead to inflammation and oxidative stress in the GI tract and thereby initiating alpha-synuclein accumulation in the ENS (Forsyth et al., 2011;Glass et al., 2010;Quigley and Quera, 2006).”

Many risk genes associated with AD mediate their effects through microglia.

“Indeed, many of the risk genes associated with AD mediate their effects through microglia, the brain‐resident macrophages (Glass et al, 2010; Heneka et al, 2015; Nott et al, 2019).”