Figure 1.

The prion-like seeding hypothesis. This theory states that like prions, misfolded disease-specific proteins may corrupt normal proteins and induce disease propagation via aggregation. One of the possible spreading mechanisms of these pathological seeds is via EVs. When in the cell, the corrupt seed may be able to induce misfolding in the endogenous proteins leading to the formation of protein aggregates that impair several key cellular pathways such as (A) clearing systems (autophagy and the UPS); (B) calcium homeostasis; (C) mitochondrial function, and (D) transcriptional dysregulation.