Microglial clearance of focal apoptotic synapses

Apoptotic cells are rarely detected in vivo because of their rapid clearance by phagocytes, suggesting that apoptosis is the cell clearance rather than cell death machinery. In consistent with this, biochemical changes associated with apoptosis including caspase-3 activation are engaged locally in synaptic compartments without neuronal death. This phenomenon is referred to as synaptic apoptosis or synaptosis, which triggers a rapid clearance of localized synaptic compartments by microglia. In this clearance system, integrin α_νβ₃/TAM receptors with bridging molecules and CR3 on microglia are essential for recognition of phosphatidylserine (PS)-exposed and C1q/C3-tagged focal synaptic compartments, respectively. Caspase-3 plays pivotal roles in both synaptic PS exposure and C1q deposition. Therefore, the accumulating knowledge concerning with focal apoptotic synapses will contribute to better understanding of synapse loss and subsequent neuronal death in neurodegenerative diseases such as Alzheimer's disease.