2,906
Views
17
CrossRef citations to date
0
Altmetric
Research Paper

Rational design of small molecules able to inhibit α-synuclein amyloid aggregation for the treatment of Parkinson’s disease

ORCID Icon, , ORCID Icon, , & ORCID Icon
Pages 1727-1735 | Received 07 Jul 2020, Accepted 21 Aug 2020, Published online: 14 Sep 2020

References

  • Chakraborty A, Brauer S, Diwan A. Possible therapies of Parkinson’s disease: a review. J Clin Neurosci 2020;75:1–4.
  • Stoker TB, Torsney KM, Barker RA. Emerging treatment approaches for Parkinson’s disease. Front Neurosci 2018;12:693.
  • Kalia LV, Lang AE. Parkinson’s disease. Lancet 2015;386:896–912.
  • Dickson DW. Parkinson’s disease and parkinsonism: neuropathology. Cold Spring Harb Perspect Med 2012;2:a009258.
  • Save SS, Rachineni K, Hosur RV, Choudhary S. Natural compound safranal driven inhibition and dis-aggregation of α-synuclein fibrils. Int J Biol Macromol 2019;141:585–95.
  • Savitt D, Jankovic J. Targeting α-synuclein in Parkinson’s disease: progress towards the development of disease-modifying therapeutics. Drugs 2019;79:797–810.
  • Afitska K, Priss A, Yushchenko DA, Shvadchak VV. Structural optimization of inhibitors of α-synuclein fibril growth: affinity to the fibril end as a crucial factor. J Mol Biol 2020;432:967–77.
  • Kyriukha YA, Afitska K, Kurochka AS, et al. α-Synuclein dimers as potent inhibitors of fibrillization. J Med Chem 2019;62:10342–51.
  • Serpell LC, Berriman J, Jakes R, et al. Fiber diffraction of synthetic alpha-synuclein filaments shows amyloid-like cross-beta conformation. Proc Natl Acad Sci USA 2000;97:4897–902.
  • Ma L, Yang C, Zheng J, et al. Non-polyphenolic natural inhibitors of amyloid aggregation. Eur J Med Chem 2020;192:112197
  • Sangwan S, Sahay S, Murray KA, et al. Inhibition of synucleinopathic seeding by rationally designed inhibitors. Elife 2020;9:e46775.
  • Haddad F, Sawalha M, Khawaja Y, et al. Dopamine and levodopa prodrugs for the treatment of Parkinson's disease. Molecules 2017;23: 40.
  • Carrera I, Cacabelos R. Current drugs and potential future neuroprotective compounds for Parkinson's disease. Curr Neuropharmacol 2019;17:295–306.
  • Borovac JA. Side effects of a dopamine agonist therapy for Parkinson's disease: a mini-review of clinical pharmacology. Yale J Biol Med 2016;89:37–47.
  • O'Hara DM, Kalia SK, Kalia LV. Emerging disease-modifying strategies targeting α-synuclein for the treatment of Parkinson's disease. Br J Pharmacol 2018;175:3080–9.
  • Peña-Díaz S, Pujols J, Conde-Giménez M, et al. ZPD-2, a small compound that inhibits α-synuclein amyloid aggregation and its seeded polymerization. Front Mol Neurosci 2019;12: 306.
  • Singh SK, Dutta A, Modi G. α-Synuclein aggregation modulation: an emerging approach for the treatment of Parkinson's disease. Future Med Chem 2017;9:1039–53.
  • Shihabuddin LS, Brundin P, Greenamyre JT, et al. New frontiers in Parkinson’s disease: from genetics to the clinic. J Neurosci 2018;38:9375–82.
  • Teil M, Arotcarena ML, Faggiani E, et al. Targeting α-synuclein for PD therapeutics: a pursuit on all fronts. Biomolecules 2020;10:391.
  • Wolber G, Langer T. LigandScout: 3-D pharmacophores derived from protein-bound ligands and their use as virtual screening filters. J Chem Inf Model 2005;45:160–9.
  • Oliveri V. Toward the discovery and development of effective modulators of α-synuclein amyloid aggregation. Eur J Med Chem 2019;167:10–36.
  • Kolodina AA, Gaponenko NI, Lesin AV. Synthesis and opening of the thiadiazine ring in 6,7-dihydro-5H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines. Russ Chem B. 2008;57:1273–6.
  • Pujols J, Peña-Díaz S, Conde-Giménez M, et al. High-throughput screening methodology to identify alpha-synuclein aggregation inhibitors. Int J Mol Sci 2017;18: 478.
  • Pujols J, Peña-Díaz S, Lázaro DF, et al. Small molecule inhibits α-synuclein aggregation, disrupts amyloid fibrils, and prevents degeneration of dopaminergic neurons. Proc Natl Acad Sci USA 2018;115:10481–6.
  • Crespo R, Villar-Alvarez E, Taboada P, et al. What can the kinetics of amyloid fibril formation tell about off-pathway aggregation? J Biol Chem 2016;291:2018–32.
  • Pedretti A, Villa L, Vistoli G. VEGA - an open platform to develop chemo-bio-informatics applications, using plug-in architecture and script programming. J Comput Aid Mol Des 2004;18:167–73.
  • Dassault Systèmes BIOVIA. BIOVIA Discovery Studio Visualizer, v20. San Diego: Dassault Systèmes; 2020.
  • Gitto R, De Luca L, Ferro S, et al. Synthesis, modelling and biological characterization of 3-substituted-1H-indoles as ligands of GluN2B-containing N-methyl-d-aspartate receptors. Bioorg Med Chem 2014;22:1040–8.
  • Morris GM, Huey R, Lindstrom W, et al. AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J Comput Chem 2009;30:2785–91.
  • Tuttle MD, Comellas G, Nieuwkoop AJ, et al. Solid-state NMR structure of a pathogenic fibril of full-length human α-synuclein. Nat Struct Mol Biol 2016;23:409–15.