The Emerging Role of the Lysosome in Parkinson’s Disease
Abstract
:1. Introduction
2. The Autophagy–Lysosomal–Endosomal System
2.1. Autophagy
2.2. Endocytosis
3. Parkinson’s Disease and Alpha-Synuclein
4. Lysosomal-Dependent Degradation of Synuclein
5. Lysosomal Dysfunction in Parkinson’s Disease
6. Lysosomal Storage Disorders and Parkinson’s Disease
7. Autophagy Dysfunction in Parkinson’s Disease
8. Endocytosis Dysfunction in Parkinson’s Disease
9. Role of Glial Cells in PD
10. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Gene | Protein | Function | LSD | Type | Evidence | Ref. |
---|---|---|---|---|---|---|
GBA | Lysosomal acid GCase | Hydrolysis of glucosylceramide into ceramide and glucose | Gaucher disease | Risk factor | +++ | [36,37,38,39,75,76,77] |
ATP13A2 | ATPase cation transporting 13A2 | Cation transporter and polyamine exporter | Neuronal ceroid lipofuscinosis | Risk factor/AR (Kufor Rakeb) | +++ | [76,78,79,80,81,82,83] |
TMEM175 | Endosomal/lysosomal potassium channel TMEM175 | Conductance of potassium in lysosomes and endosomes | Risk factor | ++ | [36,37,38,76,84] | |
SMPD1 | Sphingomyelin phosphodiesterase | Hydrolysis of sphingomyelin into ceramide | Niemann–Pick disease type A/B | Risk factor | ++ | [75,85,86,87,88] |
SCARB2 | Lysosome membrane protein 2 | Receptor for lysosomal mannose-6-phosphate-independent targeting of GCase | Action myoclonus-renal failure syndrome | Risk factor | ++ | [38,61,74,89,90,91] |
CTSD | Cathepsin D | Main aspartyl protease of the lysosome | Neuronal ceroid lipofuscinosis | Risk factor | + | [75] |
GLA | α-galactosidase A | Hydrolysis the terminal alpha-galactosyl moieties from glycolipids and glycoproteins | Fabry disease | Risk factor | + | [92] |
CTSB | Cathepsin B | Lysosomal cysteine protease | Risk factor | + | [36,37] | |
GALC | Galacto-cerebrosidase | Hydrolysis of galactose ester bonds from glycolipids | Krabbe disease | Risk factor | + | [36,37] |
ATP6V0A1 | V-ATPase 116 kDa subunit a1 | Subunit of a vacuolar ATPase that mediates acidification | Risk factor | + | [36] | |
GUSB | β-glucuronidase | Hydrolysis of glycosaminoglycans | Mucopolysaccharidosis type VII | Risk factor | + | [37] |
NEU1 | Sialidase-1 | Hydrolysis of the terminal sialic acid residues from sialylated glyco-conjugates | Sialidosis | Risk factor | + | [37] |
SLC17A5 | Sialin | Free sialic acid exporter from lysosomes | Salla disease | Risk factor | + | [75] |
ASAH1 | Acid ceramidase | Hydrolysis of sphingolipid ceramides into sphingosine and free fatty acids | Farber Lipogranulomatosis | Risk factor | + | [75] |
LAMP1 | Lysosome-associated membrane glycoprotein 1 | Trafficking of cholesterol and lipids | Risk factor | + | [76] | |
ARSA | Arylsulfatase A | Hydrolysis of cerebroside sulfate to cerebroside and sulfate | Metachromatic leukodystrophy | Risk factor/AR | + | [75,93,94] |
NPC1 | NPC intracellular cholesterol transporter 1 | Intracellular trafficking of cholesterol and lipids | Niemann-Pick type C | Risk factor | + | [95,96] |
NAGLU | α-N-acetyl glucosaminidase | Hydrolysis of terminal N-acetyl-d-glucosamine residues in N-acetyl-α-d-glucosaminides | San Filippo syndrome B | Risk factor | + | [37,97] |
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Navarro-Romero, A.; Montpeyó, M.; Martinez-Vicente, M. The Emerging Role of the Lysosome in Parkinson’s Disease. Cells 2020, 9, 2399. https://doi.org/10.3390/cells9112399
Navarro-Romero A, Montpeyó M, Martinez-Vicente M. The Emerging Role of the Lysosome in Parkinson’s Disease. Cells. 2020; 9(11):2399. https://doi.org/10.3390/cells9112399
Chicago/Turabian StyleNavarro-Romero, Alba, Marta Montpeyó, and Marta Martinez-Vicente. 2020. "The Emerging Role of the Lysosome in Parkinson’s Disease" Cells 9, no. 11: 2399. https://doi.org/10.3390/cells9112399