Caspase Gene Expression in the Brain as a Function of the Clinical Progression of Alzheimer Disease

Abstract

Proapoptotic mechanisms may be at play early in the onset of AD (before overt signs of apoptosis) and may be a conditional factor for later apoptotic cell injury or death. These data have relevance to potential therapeutic interventions for AD using selective caspase inhibitors.

Involvement of subtype 1 metabotropic glutamate receptors in apoptosis and caspase-7 over-expression in spinal cord of neuropathic rats

“…We found activation of caspase-7 in the superficial laminae of the spinal cord 3 days after sciatic nerve CCI. Consistent with our observation, a few previous reports have shown highly localized expression of caspase-7 in other brain injury paradigms [36,56].…”

Involvement of subtype 1 metabotropic glutamate receptors in apoptosis and caspase-7 over-expression in spinal cord of neuropathic rats

“…We found activation of caspase-7 in the superficial laminae of the spinal cord 3 days after sciatic nerve CCI. Consistent with our observation, a few previous reports have shown highly localized expression of caspase-7 in other brain injury paradigms [36,56].…”

Cystatin C Protects Neuronal Cells from Amyloid-β-induced Toxicity

“…The detection of cleaved caspases and the accumulation of cleaved caspase substrates in brains of AD patients support the hypothesis that apoptosis may play a role in the subsequent neuronal loss found in AD brains [49,50]. Elevated mRNA expression of several caspases was shown in the brain of AD patients compared with controls [51]. Pyramidal neurons from vulnerable regions involved in the disease showed an increase in activated caspases-3 and −6 [52,53].…”

Altered Processing of Amyloid Precursor Protein in Cells Undergoing Apoptosis

“…Due to the dogma that caspases are associated with the final stages of apoptotic cell death, the notion of caspase inhibition as a therapeutic approach in AD is sometimes regarded as “too little, too late”. However, the evidence presented here that caspase-7 is involved in APP proteolysis, as well as the previously reported observation that caspase-7 is up-regulated early in the clinical progression of dementia [16], suggests that caspase-specific inhibitors have the potential to modulate disease progression and neurodegeneration by preventing alternative processing of APP.…”

Involvement of subtype 1 metabotropic glutamate receptors in apoptosis and caspase-7 over-expression in spinal cord of neuropathic rats

“…We found activation of caspase-7 in the superficial laminae of the spinal cord 3 days after sciatic nerve CCI. Consistent with our observation, a few previous reports have shown highly localized expression of caspase-7 in other brain injury paradigms [36,56].…”

Cystatin C Protects Neuronal Cells from Amyloid-β-induced Toxicity

“…The detection of cleaved caspases and the accumulation of cleaved caspase substrates in brains of AD patients support the hypothesis that apoptosis may play a role in the subsequent neuronal loss found in AD brains [49,50]. Elevated mRNA expression of several caspases was shown in the brain of AD patients compared with controls [51]. Pyramidal neurons from vulnerable regions involved in the disease showed an increase in activated caspases-3 and −6 [52,53].…”

Altered Processing of Amyloid Precursor Protein in Cells Undergoing Apoptosis

“…Due to the dogma that caspases are associated with the final stages of apoptotic cell death, the notion of caspase inhibition as a therapeutic approach in AD is sometimes regarded as “too little, too late”. However, the evidence presented here that caspase-7 is involved in APP proteolysis, as well as the previously reported observation that caspase-7 is up-regulated early in the clinical progression of dementia [16], suggests that caspase-specific inhibitors have the potential to modulate disease progression and neurodegeneration by preventing alternative processing of APP.…”

Involvement of subtype 1 metabotropic glutamate receptors in apoptosis and caspase-7 over-expression in spinal cord of neuropathic rats

“…We found activation of caspase-7 in the superficial laminae of the spinal cord 3 days after sciatic nerve CCI. Consistent with our observation, a few previous reports have shown highly localized expression of caspase-7 in other brain injury paradigms [36,56].…”

Cystatin C Protects Neuronal Cells from Amyloid-β-induced Toxicity

“…The detection of cleaved caspases and the accumulation of cleaved caspase substrates in brains of AD patients support the hypothesis that apoptosis may play a role in the subsequent neuronal loss found in AD brains [49,50]. Elevated mRNA expression of several caspases was shown in the brain of AD patients compared with controls [51]. Pyramidal neurons from vulnerable regions involved in the disease showed an increase in activated caspases-3 and −6 [52,53].…”

Altered Processing of Amyloid Precursor Protein in Cells Undergoing Apoptosis

“…Due to the dogma that caspases are associated with the final stages of apoptotic cell death, the notion of caspase inhibition as a therapeutic approach in AD is sometimes regarded as “too little, too late”. However, the evidence presented here that caspase-7 is involved in APP proteolysis, as well as the previously reported observation that caspase-7 is up-regulated early in the clinical progression of dementia [16], suggests that caspase-specific inhibitors have the potential to modulate disease progression and neurodegeneration by preventing alternative processing of APP.…”