Neurons in Alzheimer disease emerge from senescence

Arun K. Raina, P. Pardo, Catherine Rottkamp, Xiongwei Zhu, O. M. Pereira-Smith, Mark A. Smith

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

A number of cell cycle markers are associated with the selective neuronal pathology found in Alzheimer disease. However, the significance of such cell cycle markers is clouded by duplicity of function in that many such proteins are also involved in apoptosis and/or DNA repair following oxidative damage. To clarify whether or not neurons in Alzheimer disease do in fact emerge from a quiescent status, with subsequent entry into the G1 phase of the cell cycle, in this study we focused on a family of MORF4-related proteins that are associated with emergence from senescence. Our results show that many neurons in vulnerable regions of Alzheimer disease brain, but not in control brain, have increased MORF4-related proteins indicating re-entry into the cell cycle. Immunoblot analysis showed a specific disease-related increase in a 52 kDa protein that is likely the human homologue of the MORF4-related transcription factor. The novel localization of such a transcriptional activating protein to selectively vulnerable neurons in Alzheimer disease provides compelling evidence for mitotic re-entry as part of the pathogenesis of neuronal dysfunction and death in Alzheimer disease.

Original languageEnglish (US)
Pages (from-to)3-9
Number of pages7
JournalMechanisms of Ageing and Development
Volume123
Issue number1
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

Fingerprint

Alzheimer Disease
Cell Cycle
Neurons
Proteins
Brain
G1 Phase
DNA Repair
Transcription Factors
Apoptosis
Pathology

Keywords

  • Alzheimer disease
  • Cell cycle
  • Pathogenesis

ASJC Scopus subject areas

  • Aging
  • Developmental Biology

Cite this

Neurons in Alzheimer disease emerge from senescence. / Raina, Arun K.; Pardo, P.; Rottkamp, Catherine; Zhu, Xiongwei; Pereira-Smith, O. M.; Smith, Mark A.

In: Mechanisms of Ageing and Development, Vol. 123, No. 1, 01.01.2001, p. 3-9.

Research output: Contribution to journalArticle

Raina, AK, Pardo, P, Rottkamp, C, Zhu, X, Pereira-Smith, OM & Smith, MA 2001, 'Neurons in Alzheimer disease emerge from senescence', Mechanisms of Ageing and Development, vol. 123, no. 1, pp. 3-9. https://doi.org/10.1016/S0047-6374(01)00333-5
Raina, Arun K. ; Pardo, P. ; Rottkamp, Catherine ; Zhu, Xiongwei ; Pereira-Smith, O. M. ; Smith, Mark A. / Neurons in Alzheimer disease emerge from senescence. In: Mechanisms of Ageing and Development. 2001 ; Vol. 123, No. 1. pp. 3-9.
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