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Editorial
. 2021 Sep 14:9:752378.
doi: 10.3389/fcell.2021.752378. eCollection 2021.

Editorial: Intracellular Mechanisms of α-Synuclein Processing

Friederike Zunke  1 , Beate Winner  2 , Franziska Richter  3 , Gabriela Caraveo  4
Affiliations
Editorial

Editorial: Intracellular Mechanisms of α-Synuclein Processing

Friederike Zunke et al. Front Cell Dev Biol. .
No abstract available

Keywords: alpha-synuclein; lysosomes; neurodegeneration; protein misfolding; spread; synucleinopathies.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Overview of intra- and extracellular routes of aSyn aggregation and pathology pathways as highlighted within this Research Topic: (1) Intracellular aSyn aggregation can be triggered by overexpression, post translational modifications (PTMs), or mutations within aSyn (e.g., A53T, A30P). (2–5) Pathological aSyn conformers comprising oligomers and fibrils block the autophagic/lysosomal pathway by interfering with BAG5 and the autophagic adaptor protein p62 (2), the lysosomal enzymes β-glucocerebrosidase (GBA1; 3) and cathepsin D (CTSD; 4), all critical for aSyn degradation. Dysfunction of GBA1 causes glycosphingolipids (glucosylceramide, GluCer) to increase (5). These lipids further drive aSyn aggregation. Pathological aSyn conformers also affect mitochondrial function, the lysosomal-mitochondrial crosstalk (6), vesicle recycling, and endocytosis (7), as well as formation and function of the actin cytoskeleton (8). Moreover, aSyn accumulation induces microRNAs involved in cell cycle activation (9). (10) Effects of aSyn-mediated pathologies were analyzed and summarized within different models (human, murine, C. elegans), exhibiting important roles of aSyn within the hippocampus. Additionally, aSyn is capable of escaping neurons causing cell-to-cell propagation and hence spreading of disease, which causes pathological effects on peripheral immune cells (11) and the gastro intestinal tract (GIT). The gut-brain-axis contributes to the spread of pathological aSyn conformers and disease pathology (12, 13). This illustration contains images from Servier Medical Art (smart.servier.com).
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  • Editorial on the Research Topic Intracellular Mechanisms of α-Synuclein Processing

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