How is alpha-synuclein cleared from the cell?
(2019) In Journal of Neurochemistry 150(5). p.577-590- Abstract
The levels and conformers of alpha-synuclein are critical in the pathogenesis of Parkinson's Disease and related synucleinopathies. Homeostatic mechanisms in protein degradation and secretion have been identified as regulators of alpha-synuclein at different stages of its intracellular trafficking and transcellular propagation. Here we review pathways involved in the removal of various forms of alpha-synuclein from both the intracellular and extracellular environment. Proteasomes and lysosomes are likely to play complementary roles in the removal of intracellular alpha-synuclein species, in a manner that depends on alpha-synuclein post-translational modifications. Extracellular alpha-synuclein is cleared by extracellular proteolytic... (More)
The levels and conformers of alpha-synuclein are critical in the pathogenesis of Parkinson's Disease and related synucleinopathies. Homeostatic mechanisms in protein degradation and secretion have been identified as regulators of alpha-synuclein at different stages of its intracellular trafficking and transcellular propagation. Here we review pathways involved in the removal of various forms of alpha-synuclein from both the intracellular and extracellular environment. Proteasomes and lysosomes are likely to play complementary roles in the removal of intracellular alpha-synuclein species, in a manner that depends on alpha-synuclein post-translational modifications. Extracellular alpha-synuclein is cleared by extracellular proteolytic enzymes, or taken up by neighboring cells, especially microglia and astrocytes, and degraded within lysosomes. Exosomes, on the other hand, represent a vehicle for egress of excess burden of the intracellular protein, potentially contributing to the transfer of alpha-synuclein between cells. Dysfunction in any one of these clearance mechanisms, or a combination thereof, may be involved in the initiation or progression of Parkinson's disease, whereas targeting these pathways may offer an opportunity for therapeutic intervention. (Figure presented.).
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- author
- Stefanis, Leonidas ; Emmanouilidou, Evangelia ; Pantazopoulou, Marina ; Kirik, Deniz LU ; Vekrellis, Kostas and Tofaris, George K.
- organization
- publishing date
- 2019
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- alpha-synuclein, degradation, exosomes, lysosomes, proteasome, ubiquitin
- in
- Journal of Neurochemistry
- volume
- 150
- issue
- 5
- pages
- 577 - 590
- publisher
- Wiley-Blackwell
- external identifiers
-
- pmid:31069800
- scopus:85065513129
- ISSN
- 0022-3042
- DOI
- 10.1111/jnc.14704
- language
- English
- LU publication?
- yes
- id
- 54586936-588f-44ab-a827-87b6c101c543
- date added to LUP
- 2019-06-04 12:14:12
- date last changed
- 2024-09-03 22:21:15
@article{54586936-588f-44ab-a827-87b6c101c543, abstract = {{<p>The levels and conformers of alpha-synuclein are critical in the pathogenesis of Parkinson's Disease and related synucleinopathies. Homeostatic mechanisms in protein degradation and secretion have been identified as regulators of alpha-synuclein at different stages of its intracellular trafficking and transcellular propagation. Here we review pathways involved in the removal of various forms of alpha-synuclein from both the intracellular and extracellular environment. Proteasomes and lysosomes are likely to play complementary roles in the removal of intracellular alpha-synuclein species, in a manner that depends on alpha-synuclein post-translational modifications. Extracellular alpha-synuclein is cleared by extracellular proteolytic enzymes, or taken up by neighboring cells, especially microglia and astrocytes, and degraded within lysosomes. Exosomes, on the other hand, represent a vehicle for egress of excess burden of the intracellular protein, potentially contributing to the transfer of alpha-synuclein between cells. Dysfunction in any one of these clearance mechanisms, or a combination thereof, may be involved in the initiation or progression of Parkinson's disease, whereas targeting these pathways may offer an opportunity for therapeutic intervention. (Figure presented.).</p>}}, author = {{Stefanis, Leonidas and Emmanouilidou, Evangelia and Pantazopoulou, Marina and Kirik, Deniz and Vekrellis, Kostas and Tofaris, George K.}}, issn = {{0022-3042}}, keywords = {{alpha-synuclein; degradation; exosomes; lysosomes; proteasome; ubiquitin}}, language = {{eng}}, number = {{5}}, pages = {{577--590}}, publisher = {{Wiley-Blackwell}}, series = {{Journal of Neurochemistry}}, title = {{How is alpha-synuclein cleared from the cell?}}, url = {{http://dx.doi.org/10.1111/jnc.14704}}, doi = {{10.1111/jnc.14704}}, volume = {{150}}, year = {{2019}}, }