J Mov Disord.  2019 Sep;12(3):139-151. 10.14802/jmd.19046.

Modeling α-Synuclein Propagation with Preformed Fibril Injections

• Chung HK
• Ho HA
• Pérez-Acuña D
• Lee SJ

• KMID: 2464631
• DOI: http://doi.org/10.14802/jmd.19046

Abstract

The aggregation of α-synuclein (α-syn) has been implicated in the pathogenesis of many neurodegenerative disorders, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Postmortem analyses of α-syn pathology, especially that of PD, have suggested that aggregates progressively spread from a few discrete locations to wider brain regions. The neuron-to-neuron propagation of α-syn has been suggested to be the underlying mechanism by which aggregates spread throughout the brain. Many cellular and animal models has been created to study cell-to-cell propagation. Recently, it has been shown that a single injection of preformed fibrils (PFFs) made of recombinant α-syn proteins into various tissues and organs of many different animal species results in widespread α-syn pathology in the central nervous system (CNS). These PFF models have been extensively used to study the mechanism by which aggregates spread throughout the brain. Here, we review what we have learned from PFF models, describe the nature of PFFs and the neuropathological features, neurophysiological characteristics, and behavioral outcomes of the models.

Keyword

Alpha-synuclein; Animal models; Parkinson's disease; Protein aggregation

MeSH Terms

alpha-Synuclein
Animals
Brain
Central Nervous System
Dementia
Lewy Bodies
Models, Animal
Multiple System Atrophy
Neurodegenerative Diseases
Parkinson Disease
Pathology
alpha-Synuclein