Earticle

초록

영어

Promising evidence suggests that amyloid beta peptide (Aβ), a key mediator in age-dependent neuronal and cerebrovascular degeneration, activates death signalling processes leading to neuronal as well as non-neuronal cell death in the central nervous system. A major cellular event in Aβ-induced apoptosis of non- neuronal cells, including cerebral endothelial cells, astrocytes and oligodendrocytes, is mitochondrial dysfunction. The apoptosis signalling 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, mitochondrial 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 apoptosis signalling processes will aid in the development of more effective strategies to slow down age- dependent cerebrovascular degeneration caused by progressive cerebrovascular Aβ deposition.

목차

Abstract
 1. Introduction
  1.1. Aging and Cerebrovascular Diseases
  1.2. Amyloid in the Cerebral Vasculature
  1.3. Amyloid β Peptide (Aβ)
  1.4. Aβ and Cerebrovasculature Degeneration
 2. Mitochondrial Mechanisms in Aβ-induced Non-neuronal Cell Death
  2.1. Aβ Induction of Mitochondrial Dysfunction
  2.2. The Neutral Sphingomyelinase-ceramide Cascade
  2.3. Protein Phosphatase 2A downstream of the nSMase-ceramide Cascade
  2.4. Aβ-activated Death Signalling Cascade Downstream of Mitochondria
  2.5. Other Cellular Events Relevant to Aβ-induced Cerebrovascular Degeneration
 3. Development of Pharmacological Interventions in CAA
 4. Concluding Remarks
 References

키워드

저자

• Merlin Jayalal .L .P [ Department of Biochemistry, Bharathidasan college of Arts and Science, Ellispettai, Erode-638116, Tamilnadu, India ] Corresponding author

참고문헌

발행기관

간행물

표지보기 관심저널 등록

• 간행물명

  통합자연과학논문집(구 조선자연과학논문집) [Journal of Integrative Natural Science]

• 간기

  계간

• pISSN

  2005-1042

• 수록기간

  2008~2025

• 등재여부

  KCI 등재

• 십진분류

  KDC 405 DDC 505