Microglia and Synapse: Interactions in Health and Neurodegeneration

Figure 4

The role of microglial cells in Alzheimer’s disease. Increased accumulation of Aβ peptides is thought to trigger a variety of pathological events, which subsequently compromise neuronal function. For example, Aβ molecules are known to interact with neurotransmitter receptors, disrupt synaptic and mitochondrial function, and promote neuronal proapoptotic signalling. Injured neurons release a variety of factors that together with Aβ accumulation trigger microglial activation. (a) Extracellular Aβ is taken up and degraded by microglia via receptors such as β-integrins, various enzymes including MMPs, and other uptake-mediating molecules, for example, ECE and NEP. Additionally, macrophages can degrade Aβ molecules and, together with microglia, help restrict amyloid plaque formation in the brain. These activities might represent an important recovery-promoting mechanism. (b) In response to the deposition of Aβ and the release of chemoattractants from injured neurons, activated microglia can release a range of proinflammatory mediators such as cytokines (IL-1β, IL-6, and TNF-α) and induce generation of reactive oxygen species. Although this initial response might be an attempt to protect the brain, these proinflammatory activities are believed to be a major detrimental factor, worsening the disease outcome.