Functional Links Between Aβ Toxicity, Endocytic Trafficking, and Alzheimer’s Disease Risk Factors in Yeast
Open accessAbstract
Aβ (beta-amyloid peptide) is an important contributor to Alzheimer's disease (AD). We modeled Aβ toxicity in yeast by directing the peptide to the secretory pathway. A genome-wide screen for toxicity modifiers identified the yeast homolog of phosphatidylinositol binding clathrin assembly protein (PICALM) and other endocytic factors connected to AD whose relationship to Aβ was previously unknown. The factors identified in yeast modified Aβ toxicity in glutamatergic neurons of Caenorhabditis elegans and in primary rat cortical neurons. In yeast, Aβ impaired the endocytic trafficking of a plasma membrane receptor, which was ameliorated by endocytic pathway factors identified in the yeast screen. Thus, links between Aβ, endocytosis, and human AD risk factors can be ascertained with yeast as a model system.
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Overexpression of PICALM in primary rat cortical neurons attenuated the toxicity of soluble Aβ oligomers.
“Overexpression of PICALM in the primary rat cortical neurons attenuated the toxicity of soluble A 𝛃 oligomers (598).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [598]
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- Authors
- Treusch, S., Hamamichi, S., Goodman, J. L., Matlack, K. E. S., Chung, C. Y., Baru, V., Shulman, J. M., Parrado, A., Bevis, B. J., Valastyan, J. S., Han, H., Lindhagen-Persson, M., Reiman, E. M., Evans, D. A., Bennett, D. A., Olofsson, A., DeJager, P. L., Tanzi, R. E., Caldwell, K. A., Caldwell, G. A., & Lindquist, S.
- Affiliations
- Howard Hughes Medical Institute (US)
- University of Alabama (US)
- Whitehead Institute for Biomedical Research (US)
- Broad Institute (US)
- Harvard University (US)
- Department of Medical Biochemistry and Biophysics, Umea University, Umea, Sweden.
- Translational Genomics Research Institute (US)
- Rush University Medical Center (US)
- Umeå University (SE)
- Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA.
- Corresponding author
- Lindquist, Susan
- ORCID
- Venue
- Science
- Published
- 2011-12-02
- Volume
- 334
- Issue
- 6060
- Pages
- 1241-1245
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3281757
- OpenAlex
- W2051629075
- Cited by
- 379
- References
- 59
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 13 · 2023: 21 · 2022: 14 · 2021: 20 · 2020: 26 · 2019: 36 · 2018: 27 · 2017: 23 · 2016: 22 · 2015: 32 · 2014: 36 · 2013: 36 · 2012: 52
- FWCI
- 27.49
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute on Aging (R01AG017917, P30-AG 10161, R01‐AG17917, R01 AG15819, K08AG034290, R01AG015819, P30AG010161, P30AG019610)
- National Institute of Neurological Disorders and Stroke (F32NS067782)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- amyloid-beta toxicity, Alzheimer's disease, endosomal trafficking, PICALM, yeast model, secretory pathway, plasma membrane receptors, glutamatergic neurons, Caenorhabditis elegans, cortical neurons, Alzheimer's disease risk factors
- MeSH terms
- Alzheimer Disease, Animals, Cell Membrane, Cells, Cultured, Clathrin, Cytoskeleton, Disease Susceptibility, Endocytosis, Genetic Testing, Glutamates, Humans, Neurons, Peptide Fragments, Risk Factors, Saccharomyces cerevisiae, Amyloid beta-Peptides, Caenorhabditis elegans, Protein Transport, Saccharomyces cerevisiae Proteins, Animals, Genetically Modified, Monomeric Clathrin Assembly Proteins, Rats, Protein Multimerization, Secretory Pathway, Genetic Association Studies
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