Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Sep;150(5):577-590.
doi: 10.1111/jnc.14704. Epub 2019 May 8.

How is alpha-synuclein cleared from the cell?

Leonidas Stefanis  1   2 , Evangelia Emmanouilidou  1 , Marina Pantazopoulou  1 , Deniz Kirik  3 , Kostas Vekrellis  1 , George K Tofaris  4
Affiliations
Free article
Review

How is alpha-synuclein cleared from the cell?

Leonidas Stefanis et al. J Neurochem. 2019 Sep.
Free article

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 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. This article is part of the Special Issue "Synuclein".

Keywords: alpha-synuclein; degradation; exosomes; lysosomes; proteasome; ubiquitin.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ahmed I., Liang Y., Schools S., Dawson V. L., Dawson T. M. and Savitt J. M. (2012) Development and characterization of a new Parkinson's disease model resulting from impaired autophagy. J. Neurosci. 32, 16503-16509.
    1. Alexopoulou Z., Lang J., Perrett R. M. et al. (2016) Deubiquitinase Usp8 regulates alpha-synuclein clearance and modifies its toxicity in Lewy body disease. Proc. Natl Acad. Sci. USA 113, E4688-E4697.
    1. Alvarez-Erviti L., Rodriguez-Oroz M. C., Cooper J. M., Caballero C., Ferrer I., Obeso J. A. and Schapira A. H. (2010) Chaperone-mediated autophagy markers in Parkinson disease brains. Arch. Neurol. 67, 1464-1472.
    1. Anderson J. P., Walker D. E., Goldstein J. M. et al. (2006) Phosphorylation of Ser-129 is the dominant pathological modification of alpha-synuclein in familial and sporadic Lewy body disease. J. Biol. Chem. 281, 29739-29752.
    1. Arawaka S., Sato H., Sasaki A., Koyama S. and Kato T. (2017) Mechanisms underlying extensive Ser129-phosphorylation in alpha-synuclein aggregates. Acta. Neuropathol. Commun. 5, 48.

Publication types

MeSH terms

Substances

LinkOut - more resources