Quality Over Quantity: Advantages of Using Alpha-Synuclein Preformed Fibril Triggered Synucleinopathy to Model Idiopathic Parkinson's Disease

Frontiers in Neuroscience
Megan F DuffyCaryl E Sortwell

Abstract

Animal models have significantly advanced our understanding of Parkinson's disease (PD). Alpha-synuclein (α-syn) has taken center stage due to its genetic connection to familial PD and localization to Lewy bodies, one pathological hallmark of PD. Animal models developed on the premise of elevated alpha-synuclein via germline manipulation or viral vector-mediated overexpression are used to investigate PD pathophysiology and vet novel therapeutics. While these models represented a step forward compared to their neurotoxicant model predecessors, they rely on overexpression of supraphysiological levels of α-syn to trigger toxicity. However, whereas SNCA-linked familial PD is associated with elevated α-syn, elevated α-syn is not associated with idiopathic PD. Therefore, the defining feature of the α-syn overexpression models may fail to appropriately model idiopathic PD. In the last several years a new model has been developed in which α-syn preformed fibrils are injected intrastriatally and trigger normal endogenous levels of α-syn to misfold and accumulate into Lewy body-like inclusions. Following a defined period of inclusion accumulation, distinct phases of neuroinflammation and progressive degeneration can be detected in the ni...Continue Reading

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Citations

Aug 1, 2020·Frontiers in Neuroscience·Dylan J Dues, Darren J Moore
May 12, 2020·Frontiers in Pharmacology·Mónica Gómez-BenitoRosario Moratalla
Feb 23, 2020·Proceedings of the National Academy of Sciences of the United States of America·Anne-Laure Mahul-MellierHilal A Lashuel
Nov 4, 2020·International Journal of Molecular Sciences·Zhaohui Liu, Hoi-Hung Cheung
Jun 9, 2021·Neural Regeneration Research·Susan R GouldingGerard W O'Keeffe
Oct 22, 2021·Frontiers in Cellular Neuroscience·Alix Booms, Gerhard A Coetzee

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Alpha-Synuclein Aggregation (MDS)

Alpha-synucleins are small proteins that are believed to restrict the mobility of synpatic vesicles and inhibit neurotransmitter release. Aggregation of these proteins have been linked to several types of neurodegenerative diseases including dementia with Lewy bodies and Parkinson's disease. Here is the latest research on α-synuclein aggregation.

Alpha-Synuclein Aggregation

Alpha-synucleins are small proteins that are believed to restrict the mobility of synpatic vesicles and inhibit neurotransmitter release. Aggregation of these proteins have been linked to several types of neurodegenerative diseases including dementia with Lewy bodies and Parkinson's disease. Here is the latest research on α-synuclein aggregation.