How are microglial cells activated?
How are microglial cells activated?
Microglia become activated following exposure to pathogen-associated molecular patterns (PAMPs) and/or endogenous damage-associated molecular patterns (DAMPs), and removal of the immune-suppressive signals. Activated microglia can acquire different phenotypes depending on cues in its surrounding environment.
What causes microglial activation?
In general, microglia activation is triggered by a plethora of well described subsets of immune receptors such as Toll-like receptors (TLRs), scavenger receptors, and numerous cytokine and chemokine receptors.
What activates TREM2?
TREM2 signals through its association with TYRO protein tyrosine kinase binding protein (TYROBP), also known as DNAX-activating protein of 12 kDa (DAP12), which recruits the spleen tyrosine kinase (SYK) through its cytosolic immunoreceptor tyrosine-based activation motifs (ITAMs) (Peng et al., 2010).
What is Chronic microglial activation?
Chronic microglial activation is a prominent feature of many chronic neurodegenerative diseases, including Parkinson’s and Alzheimer’s disease. To investigate the effects of chronic microglial activation on cerebellar structure and motor function throughout the lifespan, the transgenic GFAP-IL6 mouse model was used.
What are the effects of microglial TREM2 / DAP12 signaling?
Microglial TREM2/DAP12 Signaling: A Double-Edged Sword in Neural Diseases. Microglia are activated after neuronal injury and in neurodegenerative diseases, and trigger neuroinflammation in the central nervous system (CNS). Microglia-derived neuroinflammation has both beneficial and detrimental effects on neurons.
What is the activation signal of DAP12 in leukocytes?
The immunoreceptor tyrosine-based activation (ITAM) motif in the intracellular domain of some transmembrane proteins generates an activation signal in leukocytes ( Cambier, 1995 ). DAP12 was identified as an ITAM-containing, disulfide bond-linked homodimer expressed on natural killer cells ( Lanier et al., 1998 ).
Why does DAP12 have no ligand binding capability?
Because of its short extracellular domain, DAP12 itself is thought to have no ligand-binding capability. Instead, DAP12 forms complexes with some ligand-binding receptors (DAP12-associated receptors) and transduces signals from DAP12-associated receptors into the cytoplasm (Figure 1A ).
What are the roles of TREM2 / DAP12 in Alzheimer’s disease?
Furthermore, animal model studies revealed critical roles for TREM2/DAP12 in the regulation of microglial activity, including survival, phagocytosis, and cytokine production, not only in Alzheimer’s disease but also in other neural diseases, such as Parkinson’s disease, demyelinating disease, ischemia, and peripheral nerve injury.
