Although TLR4 signaling represents one of a series of immune and inflammatory factors found activated during both PD and COVID 19, the strong interaction of TLR4 with the SARS-CoV-2 S protein as well as the possible binding between SARS-CoV-2 and α-SYN suggest triggering mechanisms of neurodegenerative processes underlying PD, which deserve to be elucidated. This evidence concerns the gene TLR4 and Parkinson disease.