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A11-positive β-amyloid Oligomer Preparation and Assessment Using Dot Blotting Analysis
Published on: May 22, 2018
Role of Intracellular Amyloid β as Pathway Modulator, Biomarker, and Therapy Target
Lucia Gallego Villarejo1, Lisa Bachmann1, David Marks1
1Department of Molecular Biochemistry, Cell Signalling, Ruhr University Bochum, 44801 Bochum, Germany.
Abstract:
The β- and γ-secretase-driven cleavage of the amyloid precursor protein (APP) gives rise to the amyloid β peptide, which is believed to be the main driver of neurodegeneration in Alzheimer's disease (AD). As it is prominently detectable in extracellular plaques in post-mortem AD brain samples, research in recent decades focused on the pathological role of extracellular amyloid β aggregation, widely neglecting the potential meaning of very early generation of amyloid β inside the cell. In the last few years, the importance of intracellular amyloid β (iAβ) as a strong player in neurodegeneration has been indicated by a rising number of studies. In this review, iAβ is highlighted as a crucial APP cleavage fragment, able to manipulate intracellular pathways and foster neurodegeneration. We demonstrate its relevance as a pathological marker and shed light on initial studies aiming to modulate iAβ through pharmacological treatment, which has been shown to have beneficial effects on cognitive properties in animal models. Finally, we display the relevance of viral infections on iAβ generation and point out future directions urgently needed to manifest the potential relevance of iAβ in Alzheimer's disease.
Insights
Intracellular amyloid beta (iAβ) fragments are increasingly recognized as key drivers of Alzheimer's disease (AD) neurodegeneration. Targeting iAβ offers a promising therapeutic strategy for AD, with early studies showing cognitive benefits in animal models.
Area of Science:
- Neuroscience
- Molecular Biology
- Pathology
Background:
- Alzheimer's disease (AD) is linked to amyloid precursor protein (APP) cleavage.
- Extracellular amyloid beta (Aβ) aggregation has been the primary research focus.
- Intracellular Aβ (iAβ) is emerging as a significant factor in neurodegeneration.
Purpose of the Study:
- To highlight the critical role of iAβ in Alzheimer's disease pathogenesis.
- To review the evidence supporting iAβ as a pathological marker.
- To explore therapeutic strategies targeting iAβ.
Main Methods:
- Review of existing literature on APP cleavage and Aβ metabolism.
- Analysis of studies investigating intracellular Aβ formation and function.
- Examination of research on pharmacological interventions for iAβ.
Main Results:
- iAβ actively manipulates intracellular pathways contributing to neurodegeneration.
- iAβ serves as a relevant pathological marker for AD.
- Pharmacological modulation of iAβ shows promise in preclinical models.
Conclusions:
- Intracellular Aβ is a critical mediator of neurodegeneration in Alzheimer's disease.
- Targeting iAβ presents a novel therapeutic avenue for AD.
- Further research is needed to fully elucidate iAβ's role and therapeutic potential, including its link to viral infections.
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