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

Molecular Brain

Joo-Ok Min¹  Byung-Chul Jeong¹  Seung-Jae Lee¹  Markus Zweckstetter²  Timo Strohäker² 

[1]Department of Biomedical Sciences, Neuroscience Research Institute, Seoul National University College of Medicine

[2]German Center for Neurodegenerative Diseases (DZNE)

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

DOI  :  10.1186/s13041-022-00913-y

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown