Fig. 1

Mechanisms and roles of microglia activated by α-Syn on T cells in PD. Pathologic factors cause abnormal α-Syn accumulation in the brain parenchyma (1). Toll-like receptors on microglia can recognize misfolded α-Syn and promote the transformation of non-activated microglia into activated microglia and antigen-presenting cells (2). Proinflammatory cytokines and ROS secreted by microglia amplify neuroinflammatory responses in the brain and hasten the death of dopaminergic neurons (3). α-Syn aggregation in microglia activates NLRP3 inflammasomes, amplifying the inflammatory response and damaging dopaminergic neurons (4). The blood–brain barrier is compromised with age and disease, allowing peripheral blood immune components such as T cells to infiltrate the brain parenchyma (5). Activated microglia increase the secretion of inflammatory chemokines like RANTES and eotaxin, increasing CD8 + T cell infiltration and the cytotoxic response to dopaminergic neurons (6, 7). T lymphocyte-induced dopaminergic neuron death was mediated by the IL-17-IL-17R signaling pathway, which then activated the downstream NF-B signaling pathway (8). The images in this figure were downloaded from ProteinLounge.com with permission to use them