Correction: Defining α-synuclein species responsible for Parkinson's disease phenotypes in mice.

Multiplicity of α-Synuclein Aggregated Species and Their Possible Roles in Disease

“…These can include: slight increases in αS levels, defects in lysosome activity, oxidation and PTMs that can occur particularly in dopamine neurons, induction of the formation of intracellular αS droplets by LLPS, aberrant activity of chaperone systems or expression of other mutant genes that can impact any of the above processes. Templated recruitment of endogenous αS also occurs and, for this, particularly short fibrils appear to be the most potent αS species [75]. Multiple types of aggregates are, therefore, populated during the process of self-assembly and might be involved in different stages of the development of pathology, some species being directly involved in the induction of neurotoxicity and others in the propagation of pathology [77].…”

“…We recently published a study that compared the ability of short (50 nm) fibrils and seeding-incompetent oligomers (type-B* oligomers) to cause PD-related phenotypes in mice. Striatal injections of short fibrils or elongation-deficient oligomers caused loss of dopamine neurons in the SNc [75]. The short fibrils caused also recruitment of endogenous αS into pS129-positive inclusions that resembled LB pathology, loss of dopamine terminals in the striatum, and induction of motor behavior phenotypes.…”

“…In addition, a genome-wide association study has shown that individuals with certain polymorphisms of the SNCA gene have a higher risk of developing sporadic PD and MSA [60,72], and some of these polymorphisms have been linked to a higher expression of αS in neurons [73]. Further, the injection of αS amyloid fibrils into the brains of healthy mice induce αS inclusion formation and PD-like pathology [14,74,75].…”

“…Cell-to-cell transmission of αS aggregates has been experimentally observed [179] and more directly evidenced in grafted fetal mesencephalic neurons in PD patients after a host-to-graft αS misfolded transmission [180,181]. Indeed, the αS pathology transmission model has been used to develop cell and animal models of αS pathology as the exposure of neurons to extracellular pre-formed αS fibrils induces intracellular endogenous inclusions resembling those found in disease brains, the loss of dopaminergic neurons in the SNc and the associated motor-behavior defects, recapitulating the core features of PD [75].…”

A targetable N-terminal motif orchestrates α-Synuclein oligomer to fibril conversion

“…The aggregation landscape of αS is dynamic, involving the formation of transient oligomeric species that precede and co-exist with the final amyloid fibrils [4][5][6][7][8][9] . αS oligomers are non-fibrillar soluble species that act as key kinetic intermediates in amyloid formation6 and contribute to gain-of-toxic interactions and disruption of cellular processes 10,11 . Therefore, αS oligomers emerge as promising targets for therapeutic and diagnostic interventions 12 , particularly during the early stages of the disease.…”