TY - JOUR
T1 - Caspase Activation in Alzheimer's Disease: Early to Rise and Late to Bed
T2 - Early to rise and late to bed
AU - Rohn, Troy T.
AU - Head, Elizabeth
PY - 2008/11/1
Y1 - 2008/11/1
N2 - It has been almost 15 years since the first report of apoptosis as a major mechanism of cell death associated with Alzheimer’s disease (AD). Presently, whether neurons die through apoptosis or some other pathway is still a hotly debated issue. However, mounting evidence suggests a role for the activation of caspases and cleavage of critical cellular proteins during the progression of AD. The activation of apoptotic pathways may represent s protracted battle due to the presence of various anti-apoptotic molecules such as Bcl 2 whereby neurons do not immediately execute the apoptotic program but caspase activation occurs discretely at some low level. During this time, caspase cleavage of the amyloid-precursor protein (APP), the adaptor protein GGA3 involved with beta-amyloid production, and tau may promote the formation of beta-amyloid (Aβ) and neurofibrillary tangles (NFTs). Thus, not only may activation of caspases represent a terminal event associated with AD (i.e. cell death), but also a proximal event that promotes the pathology underlying this disease. Therefore, therapeutics aimed at preventing the activation and execution of apoptosis may provide an effective means of treating AD.
AB - It has been almost 15 years since the first report of apoptosis as a major mechanism of cell death associated with Alzheimer’s disease (AD). Presently, whether neurons die through apoptosis or some other pathway is still a hotly debated issue. However, mounting evidence suggests a role for the activation of caspases and cleavage of critical cellular proteins during the progression of AD. The activation of apoptotic pathways may represent s protracted battle due to the presence of various anti-apoptotic molecules such as Bcl 2 whereby neurons do not immediately execute the apoptotic program but caspase activation occurs discretely at some low level. During this time, caspase cleavage of the amyloid-precursor protein (APP), the adaptor protein GGA3 involved with beta-amyloid production, and tau may promote the formation of beta-amyloid (Aβ) and neurofibrillary tangles (NFTs). Thus, not only may activation of caspases represent a terminal event associated with AD (i.e. cell death), but also a proximal event that promotes the pathology underlying this disease. Therefore, therapeutics aimed at preventing the activation and execution of apoptosis may provide an effective means of treating AD.
KW - amyloid precursor protein
KW - beta-amyloid
KW - caspase
KW - mouse model
KW - Apoptosis
KW - bcl-2
KW - Neurofibrillary tangles
KW - Plaques
KW - Tau
UR - https://scholarworks.boisestate.edu/bio_facpubs/87
UR - http://dx.doi.org/10.1515/REVNEURO.2008.19.6.383
UR - http://www.scopus.com/inward/record.url?scp=60849136313&partnerID=8YFLogxK
U2 - 10.1515/REVNEURO.2008.19.6.383
DO - 10.1515/REVNEURO.2008.19.6.383
M3 - Article
C2 - 19317178
VL - 19
SP - 383
EP - 393
JO - History Faculty Publications and Presentations
JF - History Faculty Publications and Presentations
IS - 6
ER -