Autophagy in Synucleinopathy: The Overwhelmed and Defective Machinery
Abstract
:1. Introduction
2. Clinical Evidence of Autophagy Implication in Synucleinopathies
2.1. Genetic Evidence of Autophagic Involvement in Familial PD Cases
2.2. Post-Mortem Evidence of Autophagic Involvement in Synucleinopathies
3. Dual-loop Between Autophagy and α-Syn Pathogenesis
3.1. ALP Processes Participate in α-Syn Accumulation and Aggregation
3.2. ALP Pathways Participate in α-Syn Propagation
3.3. α-Syn Induces Alterations on ALP Processes
4. Role of Autophagy Impairment in Neurodegeneration
4.1. Lysosomal Dysfunction
4.2. Mitophagy Defects
4.3. Vesicular Trafficking Defects
5. Autophagy Recovery as a Therapeutic Target
5.1. mTOR-Dependent Targeting
5.2. mTOR-Independent Targeting
6. Conclusions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
α-syn | α-synuclein |
ALP | Autophagy-lysosomal pathway |
Baf | BafilomycinA1 |
CathD | Cathepsin D |
CMA | Chaperone-mediated autophagy |
CSF | Cerebrospinal fluid |
DLB | Dementia with Lewy bodies |
ER | Endoplasmic reticulum |
GABARAP | Gamma-aminobutyric acid receptor-associated protein |
GATE-16 | Golgi-associated ATPase enhancer of 16kDa |
GCase | β-glucocerebrosidase |
GCI | Glial cytoplasmic inclusions |
GD | Gaucher’s Disease |
Hsc70 | Heat-shock cognate 70kDa |
Hsp | Heat shock protein |
KO | Knock-out |
LAMP-1 | Lysosomal-associated membrane protein 1 |
LAMP-2 | Lysosomal-associated membrane protein 2 |
LB | Lewy Bodies |
LC3 | Microtubule-associated protein 1A/1B-light chain 3 |
LMX1B | LIM homeobox transcription factor 1 beta |
LN | Lewy neurites |
MA | Macroautophagy |
MEF2D | Myocyte enhancer factor 2 |
miRNA | micro RNA |
MSA | Multiple system atrophy |
P-α-syn | Phosphorylated α-synuclein |
PD | Parkinson’s Disease |
PINK1 | Phosphate and tensin homolog-induced putative kinase 1 |
ROS | Reactive oxygen species |
SN | Substantia nigra |
TFEB | Transcription factor EB |
TLR | Toll-like receptor |
WT | Wild-type |
3-MA | 3-methyladenine |
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Arotcarena, M.-L.; Teil, M.; Dehay, B. Autophagy in Synucleinopathy: The Overwhelmed and Defective Machinery. Cells 2019, 8, 565. https://doi.org/10.3390/cells8060565
Arotcarena M-L, Teil M, Dehay B. Autophagy in Synucleinopathy: The Overwhelmed and Defective Machinery. Cells. 2019; 8(6):565. https://doi.org/10.3390/cells8060565
Chicago/Turabian StyleArotcarena, Marie-Laure, Margaux Teil, and Benjamin Dehay. 2019. "Autophagy in Synucleinopathy: The Overwhelmed and Defective Machinery" Cells 8, no. 6: 565. https://doi.org/10.3390/cells8060565