Deciphering the prion-like behavior of pathogenic protein aggregates in neurodegenerative diseases

Neurodegenerative diseases are hitherto classified based on their core clinical features, the anatomical distribution of neurodegeneration, and the cell populations mainly affected. On the other hand, the wealth of neuropathological, genetic, molecular and biochemical studies have identified the existence of distinct insoluble protein aggregates in the affected brain regions. These findings have spread the use of a collective term, proteinopathy, for neurodegenerative disorders with particular type of structurally altered protein accumulation. Particularly, a recent breakthrough in this field came with the discovery that these protein aggregates can transfer from one cell to another, thereby converting normal proteins to potentially toxic, misfolded species in a prion-like manner. In this review, we focus specifically on the molecular and cellular basis that underlies the seeding activity and transcellular spreading phenomenon of neurodegeneration-related protein aggregates, and discuss how these events contribute to the disease progression.