Ectopic localization of FOXO3a protein in Lewy bodies in Lewy body dementia and Parkinson's disease

Bo Su, Haihua Liu, Xinglong Wang, Shu G. Chen, Sandra L. Siedlak, Eisaku Kondo, Raymond Choi, Atsushi Takeda, Rudy J. Castellani, George Perry, Mark A. Smith, Xiongwei Zhu, Hyoung Gon Lee

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

Lewy bodies and Lewy neurites constitute the cardinal neuropathological features of both Parkinson's disease (PD) and Lewy body dementia (LBD). Whereas α-synuclein has been found to be the major component of the Lewy body, the mechanisms by which neurons degenerate, as well as basic mechanisms involved in the formation of α-synuclein-related inclusions, remain obscure. We have suggested previously that potential mechanisms are likely to leave a "molecular signature" or protein adduct within the Lewy body, and have found examples of such signatures in previous studies. In this study, we demonstrate increased FOXO3 in association with Lewy bodies and Lewy neurites in LBD and PD brain tissue. Since FOXO proteins are involved in several pathways responsible for the regulation of cell death, cell proliferation, and cell metabolism, the ectopic localization of FOXO3 to Lewy bodies provides evidence that aberrations in basic cellular biochemistry may contribute to inclusion formation, which is likely more complex than a simple "gain of function" toxicity as is commonly opined. In light of the known interaction of FOXO3 and 14-3-3, basic protein-protein interaction between these proteins and α-synuclein may be key.

Original languageEnglish
Article number32
JournalMolecular Neurodegeneration
Volume4
Issue number1
DOIs
Publication statusPublished - 2009

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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