28 Citations (Scopus)

Abstract

Prevailing evidence suggests that amyloid beta peptide (Aβ), a key mediator in age-dependent neuronal and cerebrovascular degeneration, activates death signaling processes leading to neuronal as well as non-neuronal cell death in the central nervous system. A major cellular event in Aβ-induced death of non-neuronal cells, including cerebral endothelial cells, astrocytes and oligodendrocytes, is mitochondrial dysfunction. The death signaling cascade upstream of mitochondria entails Aβ activation of neutral sphingomyelinase, resulting in the release of ceramide from membrane sphingomyelin. Ceramide then activates protein phosphatase 2A (PP2A), a member in the ceramide-activated protein phosphatase (CAPP) family. PP2A dephosphorylation of Akt and FKHRL1 plays a pivotal role in Aβ-induced Bad translocation to mitochondria and transactivation of Bim. Bad and Bim are pro-apoptotic proteins that cause mitochondrial dysfunction characterized by excessive ROS formation, mitochnondrial DNA (mtDNA) damage, and release of mitochondrial apoptotic proteins including cytochrome c, apoptosis inducing factor (AIF), endonuclease G and Smac. The cellular events activated by Aβ to induce death of non-neuronal cells are complex. Understanding these death signaling processes will aid in the development of more effective strategies to slow down age-dependent cerebrovascular degeneration caused by progressive cerebrovascular Aβ deposition.

Original languageEnglish
Pages (from-to)290-296
Number of pages7
JournalBiochimica et Biophysica Acta - General Subjects
Volume1800
Issue number3
DOIs
Publication statusPublished - Mar 2010

Keywords

  • Aging
  • Amyloid beta peptide
  • Apoptosis
  • Ceramide
  • Cerebrovascular disease
  • Endothelial cells
  • Mitochondria
  • Stroke

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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