Home > Publications Database > Actin-nucleation promoting factor N-WASP influences alpha-synuclein condensates and pathology. > print

001     269354
005     20240808164430.0
024 7 _ |a pmc:PMC11063037
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024 7 _ |a 10.1038/s41419-024-06686-7
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100 1 _ |a Jackson, Joshua
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245 _ _ |a Actin-nucleation promoting factor N-WASP influences alpha-synuclein condensates and pathology.
260 _ _ |a London [u.a.]
|c 2024
|b Nature Publishing Group
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520 _ _ |a Abnormal intraneuronal accumulation of soluble and insoluble α-synuclein (α-Syn) is one of the main pathological hallmarks of synucleinopathies, such as Parkinson's disease (PD). It has been well documented that the reversible liquid-liquid phase separation of α-Syn can modulate synaptic vesicle condensates at the presynaptic terminals. However, α-Syn can also form liquid-like droplets that may convert into amyloid-enriched hydrogels or fibrillar polymorphs under stressful conditions. To advance our understanding on the mechanisms underlying α-Syn phase transition, we employed a series of unbiased proteomic analyses and found that actin and actin regulators are part of the α-Syn interactome. We focused on Neural Wiskott-Aldrich syndrome protein (N-WASP) because of its association with a rare early-onset familial form of PD. In cultured cells, we demonstrate that N-WASP undergoes phase separation and can be recruited to synapsin 1 liquid-like droplets, whereas it is excluded from α-Syn/synapsin 1 condensates. Consistently, we provide evidence that wsp-1/WASL loss of function alters the number and dynamics of α-Syn inclusions in the nematode Caenorhabditis elegans. Together, our findings indicate that N-WASP expression may create permissive conditions that promote α-Syn condensates and their potentially deleterious conversion into toxic species.
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650 _ 7 |a alpha-Synuclein
|2 NLM Chemicals
650 _ 7 |a Wiskott-Aldrich Syndrome Protein, Neuronal
|2 NLM Chemicals
650 _ 7 |a Actins
|2 NLM Chemicals
650 _ 7 |a WASL protein, human
|2 NLM Chemicals
650 _ 7 |a Synapsins
|2 NLM Chemicals
650 _ 7 |a Caenorhabditis elegans Proteins
|2 NLM Chemicals
650 _ 2 |a alpha-Synuclein: metabolism
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Caenorhabditis elegans: metabolism
|2 MeSH
650 _ 2 |a Wiskott-Aldrich Syndrome Protein, Neuronal: metabolism
|2 MeSH
650 _ 2 |a Actins: metabolism
|2 MeSH
650 _ 2 |a Parkinson Disease: metabolism
|2 MeSH
650 _ 2 |a Parkinson Disease: pathology
|2 MeSH
650 _ 2 |a Synapsins: metabolism
|2 MeSH
650 _ 2 |a Caenorhabditis elegans Proteins: metabolism
|2 MeSH
700 1 _ |a Hoffmann, Christian
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700 1 _ |a Scifo, Enzo
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700 1 _ |a Wang, Han
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700 1 _ |a Wischhof, Lena
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700 1 _ |a Piazzesi, Antonia
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700 1 _ |a Mondal, Mrityunjoy
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700 1 _ |a Shields, Hanna
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700 1 _ |a Zhou, Xuesi
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700 1 _ |a Mondin, Magali
|b 9
700 1 _ |a Ryan, Eanna B
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700 1 _ |a Döring, Hermann
|b 11
700 1 _ |a Prehn, Jochen H M
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700 1 _ |a Rottner, Klemens
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700 1 _ |a Giannone, Gregory
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700 1 _ |a Nicotera, Pierluigi
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700 1 _ |a Ehninger, Dan
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700 1 _ |a Milovanovic, Dragomir
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700 1 _ |a Bano, Daniele
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773 _ _ |a 10.1038/s41419-024-06686-7
|g Vol. 15, no. 4, p. 304
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|t Cell death & disease
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|x 2041-4889
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