Acidic pH promotes the formation of toxic fibrils from β-amyloid peptide
Abstract
Beta-amyloid (Abeta) peptides, the major component of senile plaques in brains of patients with Alzheimer's disease (AD), were found in the low pH organelles (i.e. endosome/lysosome) of cultured neuronal cells. Since acidic pH values have been shown to promote the self-assembly of Abetas, which seems to be a prerequisite for their neuropathogenicity, elucidating the aggregation behavior of Abetas in acidic environments and their subsequent effects on neuronal cells may be crucial for understanding the neurodegenerative process of AD. In this study, the extent and rate of aggregation of Abeta(1-42) peptides at pH values of 5.8 and 7.4, as well as the structure and neurotoxic effects of these aggregates, were examined. We showed that Abeta(1-42) peptides formed large and complex fibrils much more efficiently at acidic rather than neutral pH. Furthermore, only the pH 5.8 Abeta aggregates induced significant apoptotic death of PC12 cells, as indicated by a decrease in 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide (MTT) reduction and an increase in phosphatidylserine externalization. Taken together, our results suggest that the Abetas present in the acidic organelles may form neurotoxic fibrils more easily than those in the neutral cellular compartments.
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Microglial phagocytosis in Alzheimer disease
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- Authors
- Su, Y., & Chang, P.-T.
- Affiliations
- National Yang Ming University (TW)
- Corresponding author
- Su, Yeu
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2001-03
- Volume
- 893
- Issue
- 1-2
- Pages
- 287-291
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W2167587239
- Cited by
- 135
- References
- 3
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 11 · 2023: 9 · 2022: 6 · 2021: 10 · 2020: 13 · 2019: 4 · 2018: 5 · 2017: 8 · 2016: 5 · 2015: 7 · 2014: 8 · 2013: 2 · 2012: 6
- FWCI
- 1.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Council
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- beta-amyloid peptide, amyloid-beta 42, low pH, fibril formation, amyloid fibril formation, Alzheimer's disease, neurotoxicity, apoptosis, PC12 cells, lysosomes, endosomes, phosphatidylserine exposure, amyloid plaques
- MeSH terms
- Acids, Amyloid, Animals, Cell Survival, Fluorescent Dyes, Hydrogen-Ion Concentration, Microscopy, Fluorescence, Peptide Fragments, Phosphatidylserines, Tetrazolium Salts, Thiazoles, Amyloid beta-Peptides, PC12 Cells, Apoptosis, Macromolecular Substances, Rats
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