Parkinson’s disease(PD),the second most common age-associated neurodegenerative disorder,is characterized by the loss of dopaminergic(DA)neurons and the presence ofα-synuclein-containing aggregates in the substantia nigra pars compacta(SNpc).Chronic neuroinflammation is one of the hallmarks of PD pathophysiology.Postmortem analyses of human PD patients and experimental animal studies indicate that activation of glial cells and increases in pro-inflammatory factor levels are common features of the PD brain.Chronic release of proinflammatory cytokines by activated astrocytes and microglia leads to the exacerbation of DA neuron degeneration in the SNpc.Besides,peripheral immune system is also implicated in the pathogenesis of PD.Infiltration and accumulation of immune cells from the periphery are detected in and around the affected brain regions of PD patients.Moreover,inflammatory processes have been suggested as promising interventional targets for PD and even other neurodegenerative diseases.A better understanding of the role of inflammation in PD will provide new insights into the pathological processes and help to establish effective therapeutic strategies.In this review,we will summarize recent progresses in the neuroimmune aspects of PD and highlight the potential therapeutic interventions targeting neuroinflammation.
Postmitotic neurons in the neocortex migrate to appropriate positions and form layered structures of nascent cortex during brain development. The migration of these neurons requires precise control and coordination of a large number of molecules such as axon guidance cues. The Eph-ephrin signaling pathway plays important roles in the development of the nervous system in a wide variety of ways, including cell segregation, axon pathfinding, and neuron migration. However, the role of ephrin-B2/ EphA4 signaling in cortical neuron migration remains elusive. Here we demonstrated that ephrin-B2 and its receptor EphA4 were expressed in complementary and overlapping patterns in the developing neocortex. Deletion of the EphA4 gene in the embryonic cerebral cortex resulted in faster migration of cortical neurons, whereas knockdown or overexpression of ephdn-B2 did not alter the normal process of migration. These results suggest that ephrin-B2 forward signaling through EphA4 is required for the precise control of cortical neuron migration.
