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Alpha-synuclein: prion or prion-like?

  • Rehana K. LeakEmail author
  • Matthew P. Frosch
  • Thomas G. Beach
  • Glenda M. Halliday
Commentary Letter

Misfolded alpha-synuclein is a corruptive seed, but is it infectious?

Alpha-synuclein is a natively unfolded or intrinsically disordered protein, but it can also assume amphipathic alpha-helical shapes in the presence of negatively charged lipids. In Lewy body disorders, alpha-synuclein monomers aggregate into oligomers, protofibrils, and fibrils, forming part of the hallmark amyloid inclusions known as Lewy bodies and Lewy neurites. Proteins exist in biological settings in multiple conformations, often with varied biological functions, and the transitions between conformations include structures that seed the nucleated growth of aggregates [10]. After the kinetic barrier to aggregation of natively monomeric proteins is (rarely) overcome, the global free-energy minimum favors the precipitation of hydrophobically packed protein masses [15]. Once this low-energy state is acquired, it may not be energetically feasible to proteolyze and resolve the protein mass, and therefore, “the...

Notes

Acknowledgements

We apologize to those authors whose work we had no room to cite. This commentary was supported by National Institutes of Health (NIH) Grants 1R15NS093539 and 1R21NS107960 to Rehana Leak. Additional support was provided by NIH Grants P30AG062421 to Matthew Frosch, NIH Grants U24NS072026 and P30AG19610 to Thomas Beach, and National Health and Medical Research Council (NHMRC) Grant #1079679 to Senior Principal Research Fellow Glenda Halliday. The authors declare no conflicts of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Pharmaceutical Sciences Division, Graduate School of Pharmaceutical SciencesDuquesne UniversityPittsburghUSA
  2. 2.C.S. Kubik Laboratory for NeuropathologyMassachusetts General HospitalBostonUSA
  3. 3.Civin Laboratory for NeuropathologyBanner Sun Health Research InstituteSun CityUSA
  4. 4.Brain and Mind Centre and Central Clinical SchoolUniversity of SydneySydneyAustralia

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