2. Academic Validation
  3. Chicago sky blue 6B inhibits α-synuclein aggregation and propagation

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

  • Mol Brain. 2022 Mar 28;15(1):27. doi: 10.1186/s13041-022-00913-y.
Joo-Ok Min 1,  Timo Strohäker 2,  Byung-Chul Jeong 1 3,  Markus Zweckstetter 2 4,  Seung-Jae Lee 5
Affiliations

Affiliations

  • 1 Department of Biomedical Sciences, Neuroscience Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongro-gu, Seoul, 03080, Republic of Korea.
  • 2 German Center for Neurodegenerative Diseases (DZNE), Von-Siebold-Str. 3a, 37075, Göttingen, Germany.
  • 3 Nutritional Sciences and Toxicology Department, University of California Berkeley, Berkeley, USA.
  • 4 Department for NMR-Based Structural Biology, Max Planck Institute for Biophysical Chemistry, Am Faßberg 11, 37077, Göttingen, Germany.
  • 5 Department of Biomedical Sciences, Neuroscience Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongro-gu, Seoul, 03080, Republic of Korea. sjlee66@snu.ac.kr.
PMID: 35346306 DOI: 10.1186/s13041-022-00913-y
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.

Keywords

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

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z