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Comment
. 2017 Feb 7;114(6):1223-1225.
doi: 10.1073/pnas.1620159114. Epub 2017 Jan 26.

Modulating membrane binding of α-synuclein as a therapeutic strategy

André Pineda  1 , Jacqueline Burré  2
Affiliations
Comment

Modulating membrane binding of α-synuclein as a therapeutic strategy

André Pineda et al. Proc Natl Acad Sci U S A. .
No abstract available

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Physiological and pathological conformations of α-synuclein and strategies to combat α-synuclein aggregation and toxicity. Physiologically, α-synuclein exists in an equilibrium between α-helical multimers bound to synaptic vesicles, and a natively unfolded monomeric state. Membranous α-synuclein clusters synaptic vesicles and chaperones SNARE complex assembly to maintain neurotransmitter release. Under pathological conditions, partial membrane binding of α-synuclein increases the local concentration of the aggregation-prone NAC region, allowing seeding of α-synuclein aggregation. Similarly, cytosolic monomeric α-synuclein spontaneously forms oligomers, which eventually build up as amyloid fibrils and spread to neurons and glia in a prion-like manner. Various therapeutic strategies are being pursued to prevent α-synuclein–mediated pathology, by modulating α-synuclein aggregation, transsynaptic spread, or membrane binding.
See this image and copyright information in PMC

Comment on

  • A natural product inhibits the initiation of α-synuclein aggregation and suppresses its toxicity.
    Perni M, Galvagnion C, Maltsev A, Meisl G, Müller MB, Challa PK, Kirkegaard JB, Flagmeier P, Cohen SI, Cascella R, Chen SW, Limbocker R, Sormanni P, Heller GT, Aprile FA, Cremades N, Cecchi C, Chiti F, Nollen EA, Knowles TP, Vendruscolo M, Bax A, Zasloff M, Dobson CM. Perni M, et al. Proc Natl Acad Sci U S A. 2017 Feb 7;114(6):E1009-E1017. doi: 10.1073/pnas.1610586114. Epub 2017 Jan 17. Proc Natl Acad Sci U S A. 2017. PMID: 28096355 Free PMC article.

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