Cell cycle aberrations by α-synuclein over-expression and cyclin B immunoreactivity in Lewy bodies

S. S. Lee, Y. M. Kim, Eunsung Junn, G. Lee, K. H. Park, M. Tanaka, R. D. Ronchetti, M. M. Quezado, M Maral Mouradian

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

α-Synuclein is a presynaptic protein that accumulates abnormally in Lewy bodies of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Its physiological function and role in neuronal death remain poorly understood. Recent immunohistochemical studies suggest that cell cycle-related phenomena may play a role in the pathogenesis of Alzheimer's disease and perhaps other neurodegenerative disorders. In this investigation, we examined the effects of α-synuclein expression levels on cell cycle indices in PC12 cells engineered to conditionally induce α-synuclein expression upon withdrawal of doxycycline. Over-expression of α-synuclein resulted in enhanced proliferation rate and enrichment of cells in the S phase of the cell cycle. This was associated with increased accumulation of the mitotic factor cyclin B and down-regulation of the tumor suppressor retinoblastoma 2. Additionally, ERK1/2, key molecules in proliferation signaling, were highly phosphorylated. Immunohistochemical studies on postmortem brains revealed intense cyclin B immunoreactivity in Lewy bodies in cases with DLB and to a lesser extent in PD. We propose that elevated expression of α-synuclein causes changes in cell cycle regulators through ERK activation leading to apoptosis of postmitotic neurons. These changes in cell cycle proteins are also associated with ectopic expression of cyclin B in Lewy bodies.

Original languageEnglish (US)
Pages (from-to)687-696
Number of pages10
JournalNeurobiology of Aging
Volume24
Issue number5
DOIs
StatePublished - Sep 1 2003

Fingerprint

Synucleins
Cyclin B
Lewy Bodies
Cell Cycle
Lewy Body Disease
Parkinson Disease
Cell Cycle Proteins
Retinoblastoma
Doxycycline
PC12 Cells
S Phase
Neurodegenerative Diseases
Alzheimer Disease
Down-Regulation
Apoptosis
Neurons
Brain
Neoplasms
Proteins

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Geriatrics and Gerontology
  • Aging
  • Neuroscience(all)
  • Developmental Biology

Cite this

Lee, S. S. ; Kim, Y. M. ; Junn, Eunsung ; Lee, G. ; Park, K. H. ; Tanaka, M. ; Ronchetti, R. D. ; Quezado, M. M. ; Mouradian, M Maral. / Cell cycle aberrations by α-synuclein over-expression and cyclin B immunoreactivity in Lewy bodies. In: Neurobiology of Aging. 2003 ; Vol. 24, No. 5. pp. 687-696.
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Cell cycle aberrations by α-synuclein over-expression and cyclin B immunoreactivity in Lewy bodies. / Lee, S. S.; Kim, Y. M.; Junn, Eunsung; Lee, G.; Park, K. H.; Tanaka, M.; Ronchetti, R. D.; Quezado, M. M.; Mouradian, M Maral.

In: Neurobiology of Aging, Vol. 24, No. 5, 01.09.2003, p. 687-696.

Research output: Contribution to journalArticle

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