TLR4 and Parkinson disease: In PD, abnormal aggregation of α-synucleinactivates toll-likereceptor 4 (TLR4), releasing pro-inflammatory cytokines and causingfatigue symptoms.54 Chronic peripheralinflammation and immune activation responses induce elevated levelsof pro-inflammatory cytokines, which can cross the BBB and contributeto the occurrence of fatigue.