MAPT and nervous system disorder: Accordingly, in this study, we found that despite its high molecular weight (over 90 kDa), systemically administered plasminogen rapidly crossed the BBB, enhanced plasmin activity, entered the cells and accumulated in the nucleus, and significantly promoted α-syn, Tau and TDP-43 clearance in vitro, ex vivo and in vivo; we observed similar results in other neurological disease models17.