Apoptotic promoters and inhibitors in Alzheimer's disease: Who wins out?
A spectrum of apoptotic mediators are seen in neurons that are vulnerable in Alzheimer's disease (AD), leading many investigators to suggest that neuronal death in AD is mediated by an apoptotic process. Indeed, the environment of the AD brain is awash with proapoptotic mediators including amyloid-beta, oxidative stress, hydroxynonenal oxidants and metabolic alterations with concomitant energy failures. However, the phenotype that defines the terminal events that are pathogonomic of apoptosis, such as chromatin condensation, apoptotic bodies and membrane blebbing, are not seen in AD. Therefore, we speculated that, although AD presents with a proapoptotic environment, apoptosis does not proceed to completion. In this regard, we found that while the initiator phases of apoptosis were engaged, this does not lead to the activation of the terminal commitment phase necessary for apoptotic cell death. In other words, in AD, there is a lack of effective apoptotic signal propagation to distal effectors. This is a novel phenomenon (which we term abortosis) that represents an inhibition of apoptosis at the postinitiator stage in neurons that survive in AD.
Raina
Arun K
AK
Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, 44106, Cleveland, OH, USA.
Hochman
Ayala
A
Ickes
Harold
H
Zhu
Xiongwei
X
Ogawa
Osamu
O
Cash
Adam D
AD
Shimohama
Shun
S
Perry
George
G
Smith
Mark A
MA
D000544:Alzheimer Disease / Q000188:drug therapy / Q000473:pathology*; D017209:Apoptosis / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D003864:Depression, Chemical; D006801:Humans; D013268:Stimulation, Chemical