Naphthoquinone–Dopamine Hybrids Inhibit α‐Synuclein Aggregation, Disrupt Preformed Fibrils, and Attenuate Aggregate‐Induced Toxicity - Archive ouverte HAL Access content directly
Journal Articles Chemistry - A European Journal Year : 2020

Naphthoquinone–Dopamine Hybrids Inhibit α‐Synuclein Aggregation, Disrupt Preformed Fibrils, and Attenuate Aggregate‐Induced Toxicity

(1) , (1) , (2) , (3) , (2) , (1) , (1)
1
2
3
Ashim Paul
  • Function : Author
Adi Huber
  • Function : Author
Daniel Rand
Ehud Gazit
  • Function : Author
Daniel Segal
  • Function : Correspondent author
  • PersonId : 1089844

Connectez-vous pour contacter l'auteur

Abstract

Accumulation and aggregation of the intrinsically disordered protein α‐synuclein (α‐Syn) into amyloid fibrils are hallmarks of a series of heterogeneous neurodegenerative disorders, known as synucleinopathies and most notably Parkinson's disease (PD). The crucial role of α‐Syn aggregation in PD makes it an attractive target for the development of disease‐modifying therapeutics that would inhibit α‐Syn aggregation or disrupt its preformed fibrillar assemblies. To this end, we have designed and synthesized two naphthoquinone–dopamine‐based hybrid small molecules, NQDA and Cl‐NQDA, and demonstrated their ability to inhibit in vitro amyloid formation by α‐Syn using ThT assay, CD, TEM, and Congo red birefringence. Moreover, these hybrid molecules efficiently disassembled preformed fibrils of α‐Syn into nontoxic species, as evident from LUV leakage assay. NQDA and Cl‐NQDA were found to have low cytotoxicity and they attenuated the toxicity induced by α‐Syn towards SH‐SY5Y neuroblastoma cells. NQDA was found to efficiently cross an in vitro human blood–brain barrier model. These naphthoquinone–dopamine based derivatives can be an attractive scaffold for therapeutic design towards PD.
Fichier principal
Vignette du fichier
Paul et al-Revised Manuscript.pdf (1.17 Mo) Télécharger le fichier
Origin : Files produced by the author(s)

Dates and versions

hal-03126960 , version 1 (19-07-2022)

Identifiers

Cite

Ashim Paul, Adi Huber, Daniel Rand, Fabien Gosselet, Itzik Cooper, et al.. Naphthoquinone–Dopamine Hybrids Inhibit α‐Synuclein Aggregation, Disrupt Preformed Fibrils, and Attenuate Aggregate‐Induced Toxicity. Chemistry - A European Journal, 2020, 26 (69), pp.16486-16496. ⟨10.1002/chem.202003374⟩. ⟨hal-03126960⟩

Collections

UNIV-ARTOIS LBHE
31 View
24 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More