Fig. 9

VCP regulation of tau seeding. VCP regulates endolysosomal integrity, which governs the amount of tau seeds escaping into the cytoplasm. VCP then acts on tau seeds that enter the cytoplasm to promote or inhibit either their degradation or amplification. Disaggregase activity of VCP removes monomer for degradation. This might occur at the end of filaments, which would decrease seeding, or from within, which could fragment fibrils and promote seeding. Chemical inhibitors and cofactors bias the process towards different paths