Deciphering the prion-like behavior of pathogenic protein aggregates in neurodegenerative diseases. (May 2022)

• Record Type: Journal Article
• Authors: Yoshida, Shun; Hasegawa, Takafumi
• Is Part Of: Neurochemistry international. Volume 155(2022)
• Publication Date: 2022-05
• Subjects: Prion-like transmission -- Protein aggregates -- Alzheimer's disease -- Parkinson's disease -- Amyotrophic lateral sclerosis -- Huntington's disease; Neurochemistry -- Periodicals; Neurochemistry -- Periodicals; Neurochimie -- Périodiques; Neurochemistry; Periodicals; 612.804205
• DOI: 10.1016/j.neuint.2022.105307
• Languages: English
• ISSNs: 0197-0186

Abstract

Abstract: 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. Highlights: Formation of misfolded protein aggregates in the nervous system is a key hallmark of common neurodegenerative diseases. Evidence indicates that non-prion aggregates can also transmit between cells and seed the misfolding of their normal conformers. The molecular and cellular mechanisms of prion-like transmission may differ based on the biochemical nature of protein aggregates and cell-autonomous/non-cell-autonomous circumstances.