How is alpha‐synuclein cleared from the cell?
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 traffick...
| Main Authors: | , , , , , |
|---|---|
| Format: | Journal article |
| Sprog: | English |
| Udgivet: |
Wiley
2019
|
| _version_ | 1826283751421771776 |
|---|---|
| author | Stefanis, L Emmanouilidou, E Pantazopoulou, M Kirik, D Vekrellis, K Tofaris, GK |
| author_facet | Stefanis, L Emmanouilidou, E Pantazopoulou, M Kirik, D Vekrellis, K Tofaris, GK |
| author_sort | Stefanis, L |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T01:03:37Z |
| format | Journal article |
| id | oxford-uuid:8a8efac0-6d2d-43d6-b40d-c8e6a45c5ea8 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:03:37Z |
| publishDate | 2019 |
| publisher | Wiley |
| record_format | dspace |
| spelling | oxford-uuid:8a8efac0-6d2d-43d6-b40d-c8e6a45c5ea82022-03-26T22:32:25ZHow is alpha‐synuclein cleared from the cell?Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:8a8efac0-6d2d-43d6-b40d-c8e6a45c5ea8EnglishSymplectic Elements at OxfordWiley2019Stefanis, LEmmanouilidou, EPantazopoulou, MKirik, DVekrellis, KTofaris, GKThe 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. |
| spellingShingle | Stefanis, L Emmanouilidou, E Pantazopoulou, M Kirik, D Vekrellis, K Tofaris, GK How is alpha‐synuclein cleared from the cell? |
| title | How is alpha‐synuclein cleared from the cell? |
| title_full | How is alpha‐synuclein cleared from the cell? |
| title_fullStr | How is alpha‐synuclein cleared from the cell? |
| title_full_unstemmed | How is alpha‐synuclein cleared from the cell? |
| title_short | How is alpha‐synuclein cleared from the cell? |
| title_sort | how is alpha synuclein cleared from the cell |
| work_keys_str_mv | AT stefanisl howisalphasynucleinclearedfromthecell AT emmanouilidoue howisalphasynucleinclearedfromthecell AT pantazopouloum howisalphasynucleinclearedfromthecell AT kirikd howisalphasynucleinclearedfromthecell AT vekrellisk howisalphasynucleinclearedfromthecell AT tofarisgk howisalphasynucleinclearedfromthecell |