Related Experiment Video
Updated: May 4, 2026
Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
Published on: March 5, 2018
Amyloid β binds procaspase-9 to inhibit assembly of Apaf-1 apoptosome and intrinsic apoptosis pathway
Md Golam Sharoar1, Md Imamul Islam2, Md Shahnawaz3
1Department of Bio-Materials Engineering, College of Medicine, Chosun University, Gwangju 501-759, Republic of Korea; Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi 6205, Bangladesh.
Abstract:
Apoptosis is essential in the death process induced by Amyloid-β (Aβ), a major constituent of diffuse plaques found in Alzheimer's disease patients. However, we have found that caspase activation and cell death induced by staurosporine, employed to induce the intrinsic mitochondria-dependent apoptotic pathway, were significantly reduced by 42 amino-acid Aβ42, implying that the peptide also has a negative effect on the apoptotic process. The inhibitory effect of Aβ42 on the apoptotic pathway is associated with its interaction with procaspase-9 and consequent inhibition of Apaf-1 apoptosome assembly. We detected the inhibitory effect in the early stage (<8h) of apoptosis, but later caspase activation becomes obvious. Thus we inferred that the inhibitory process on apoptosis begins at an early stage, and the later robust activation surpasses it. We propose that the apoptotic manifestation in Aβ-treated cells is a combined consequence of those anti- and pro-apoptotic processes.
Insights
Amyloid-beta (Aβ) peptide paradoxically inhibits early apoptosis initiation by blocking caspase-9 and apoptosome assembly, yet cells later overcome this, leading to combined anti- and pro-apoptotic effects in Alzheimer's disease.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Alzheimer's disease (AD) is characterized by amyloid-beta (Aβ) plaques.
- Apoptosis, or programmed cell death, is a key process implicated in AD pathogenesis.
- The precise role of Aβ in modulating apoptosis remains complex and requires further elucidation.
Purpose of the Study:
- To investigate the effect of Aβ42 on the intrinsic mitochondrial apoptotic pathway.
- To determine the molecular mechanisms underlying Aβ42's influence on apoptosis.
- To understand the dual role of Aβ in cellular death processes.
Main Methods:
- Induction of apoptosis using staurosporine to activate the intrinsic pathway.
- Assessment of caspase activation and cell death.
- Analysis of procaspase-9 interaction and Apaf-1 apoptosome assembly.
Main Results:
- Aβ42 significantly reduced staurosporine-induced caspase activation and cell death in early apoptosis (<8h).
- Aβ42 was found to interact with procaspase-9, inhibiting Apaf-1 apoptosome assembly.
- Later caspase activation was observed, suggesting a temporal shift in apoptotic response.
Conclusions:
- Aβ42 exerts an early inhibitory effect on apoptosis by interfering with key components of the intrinsic pathway.
- This inhibition is overcome by later, robust caspase activation, leading to a complex apoptotic outcome.
- The overall apoptotic manifestation in Aβ-treated cells results from a combination of anti- and pro-apoptotic processes.
Related Concept Videos
01:31The Intrinsic Apoptotic Pathway
01:24Caspases
01:17The Extrinsic Apoptotic Pathway
01:30Apoptosis
03:03Amyloid Fibrils
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
03:03Amyloid Fibrils