Chicago sky blue 6B inhibits α-synuclein aggregation and propagation

Joo Ok Min, Timo Strohäker, Byung Chul Jeong, Markus Zweckstetter, Seung Jae Lee

Research output: Contribution to journalArticlepeer-review

Abstract

Abnormal deposition of α-synuclein aggregates in Lewy bodies and Lewy neurites is the hallmark lesion in Parkinson’s disease (PD). These aggregates, thought to be the culprit of disease pathogenesis, spread throughout the brain as the disease progresses. Agents that inhibit α-synuclein aggregation and/or spread of aggregates would thus be candidate disease-modifying drugs. Here, we found that Chicago sky blue 6B (CSB) may be such a drug, showing that it inhibits α-synuclein aggregation and cell-to-cell propagation in both in vitro and in vivo models of synucleinopathy. CSB inhibited the fibrillation of α-synuclein in a concentration-dependent manner through direct binding to the N-terminus of α-synuclein. Furthermore, both seeded polymerization and cell-to-cell propagation of α-synuclein were inhibited by CSB treatment. Notably, CSB alleviated behavioral deficits and neuropathological features, such as phospho-α-synuclein and astrogliosis, in A53T α-synuclein transgenic mice. These results indicate that CSB directly binds α-synuclein and inhibits its aggregation, thereby blocking α-synuclein cell-to-cell propagation.

Original languageEnglish
Article number27
JournalMolecular brain
Volume15
Issue number1
DOIs
StatePublished - Dec 2022

Keywords

  • Aggregate propagation
  • Chicago sky blue 6B
  • Parkinson’s disease
  • Protein aggregation
  • α-synuclein

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