Alzheimer’s Disease is a neurodegenerative disorder. An indicating factor of Alzheimer’s Disease (AD) is beta-amyloid plaques (Aß). These plaques are known as senile plaques. They clutter the brain and slow the neural response. Senile plaques also interrupt the firing of signals between neurons. The response between neurons can be delayed by a significant amount of time by the build-up of these Aß plaques. Microglia are part of the brain’s immune system. They help to rid the brain of waste, such as apoptotic cells, and to fight infections. Triggering receptors expressed on myeloid cells 2 (TREM2) are part of the signaling mechanism that tells the microglia to do its job and remove Aß plaques. TREM2 increases the presence of CD36, which is a gene that helps microglia ingest the Aß, in microglia.
Membrane Structure & Function:
Microglia cells is part of the central nervous system’s immune function. They are a part of a group of cells called glial cells which help to maintain homeostasis in the central nervous system (1). Glial cells are eukaryotic cells since they have a nucleus. There are calcium-binding proteins in the membrane of the microglia cell. There are also proteins that play a role in the inflammation process, as well as microtubule network assembly. Microglia use endocytosis to remove debris and dead or damaged cells and transport it outside of the brain. Microglia specifically remove the Aß plaques in a “normal” functioning brain. In an Alzheimer’s Disease brain, the response from microglia is interrupted, which leads to the build-up of Aß plaques in the brain.
G-coupled protein receptors are involved in signaling microglia. The specific type is G-coupled protein receptor 84. GPR84 is an activator of motility in microglia. This suggests that GPR84 could be used as a therapeutic target in microglia-related diseases such as Alzheimer’s Disease. Aß oligomers stimulate a tyrosine kinase signaling response in microglia. This leads microglia to activate and begin its immune response within the brain; i.e. cleaning up of debris, such as apoptotic cells, and removing viruses and bacteria from the brain (2).
Microglia cells use aerobic metabolism in the form of oxidative phosphorylation for energy production. In the M1 polarization state, microglia cells shift from oxidative phosphorylation to glycolysis. The reason that this occurs is because microglia modify their metabolic functions from a growth-promoting capacity (M2) to a killing/inhibitory capacity (M1). This allows them to respond with appropriate functions in distinct context.