Baicalein reduces E46K α-synuclein aggregation in vitro and protects cells against E46K α-synuclein toxicity in cell models of familiar Parkinsonism

Mali Jiang, Yair Porat-Shliom, Zhong Pei, Yong Cheng, Lan Xiang, Katherine Sommers, Qing Li, Frank Gillardon, Bastian Hengerer, Cynthia Berlinicke, Wanli W. Smith, Donald J. Zack, Michelle A. Poirier, Christopher A. Ross, Wenzhen Duan

Research output: Contribution to journalArticlepeer-review

Abstract

The E46K is a point mutation in α-synuclein (α-syn) that causes familial Parkinsonism with Lewy body dementia. We have now generated a cell model of Parkinsonism/Parkinson's disease (PD) and demonstrated cell toxicity after expression of E46K in the differentiated PC12 cells. E46K α-syn inhibited proteasome activity and induced mitochondrial depolarization in the cell model. Baicalein has been reported to inhibit fibrillation of wild type α-syn in vitro, and to protect neurons against several chemical-induced models of PD. We now report that baicalein significantly attenuated E46K-induced mitochondrial depolarization and proteasome inhibition, and protected cells against E46K-induced toxicity in a cell model of PD. Baicalein also reduced E46K fibrilization in vitro, with a concentration-dependent decrease in beta sheet conformation, though it increased some oligomeric species, and decreased formation of E46K α-syn-induced aggregates and rescued toxicity in N2A cells. Taken together, these data indicate that mitochondrial dysfunction, proteasome inhibition and specific aspects of abnormal E46K aggregation accompany E46K α-syn-induced cell toxicity, and baicalein can protect as well as altering aggregation properties. Baicalein has potential as a tool to understand the relation between different aggregation species and toxicity, and might be a candidate compound for further validation by using in vivoα-syn genetic PD models.

Original languageEnglish (US)
Pages (from-to)419-429
Number of pages11
JournalJournal of Neurochemistry
Volume114
Issue number2
DOIs
StatePublished - Jul 2010

Keywords

  • Parkinson's disease
  • aggregation
  • baicalein
  • mitochondria depolarization
  • proteasome inhibition
  • α-synuclein

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Baicalein reduces E46K α-synuclein aggregation in vitro and protects cells against E46K α-synuclein toxicity in cell models of familiar Parkinsonism'. Together they form a unique fingerprint.

Cite this