ArticleBiochimica et biophysica acta2013
Suppression of Aβ toxicity by puromycin-sensitive aminopeptidase is independent of its proteolytic activity.
Article in Biochimica et biophysica acta, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 18 citations in OpenAlex.
- Brain Hydrophobic Peptides Antagonists of Neurotoxic Amyloid β Peptide Monomers/Oligomers-Protein Interactions.International journal of molecular sciences · 2023Review
- Beneficial effects of physical exercise and an orally active mGluR2/3 antagonist pro-drug on neurogenesis and behavior in an Alzheimer's amyloidosis model.Frontiers in dementia · 2023Article
- Contribution of proteases to the hallmarks of aging and to age-related neurodegeneration.Aging cell · 2022Review
- Exploring Aβ Proteotoxicity and Therapeutic Candidates UsingInternational journal of molecular sciences · 2021Review
- Aminobenzosuberone Scaffold as a Modular Chemical Tool for the Inhibition of Therapeutically Relevant M1 Aminopeptidases.Molecules (Basel, Switzerland) · 2018Article
- UsingBioMed research international · 2018Review
- Planarian homolog of puromycin-sensitive aminopeptidase DjPsa is required for brain regeneration.Invertebrate neuroscience : IN · 2017Article
- Icariside II, a Broad-Spectrum Anti-cancer Agent, Reverses Beta-Amyloid-Induced Cognitive Impairment through Reducing Inflammation and Apoptosis in Rats.Frontiers in pharmacology · 2017Article
- Metabolic changes may precede proteostatic dysfunction in a Drosophila model of amyloid beta peptide toxicity.Neurobiology of aging · 2016Article
- Modeling the complex pathology of Alzheimer's disease in Drosophila.Experimental neurology · 2015Review
- Iron is a specific cofactor for distinct oxidation- and aggregation-dependent Aβ toxicity mechanisms in a Drosophila model.Disease models & mechanisms · 2015Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
The accumulation of β-amyloid (Aβ) peptide in the brain is one of the pathological hallmarks of Alzheimer's disease and is thought to be of primary aetiological significance. In an unbiased genetic screen, we identified puromycin-sensitive aminopeptidase (PSA) as a potent suppressor of Aβ toxicity in a Drosophila model system. We established that coexpression of Drosophila PSA (dPSA) in the flies' brains improved their lifespan, protected against locomotor deficits, and reduced brain Aβ levels by clearing the Aβ plaque-like deposits. However, confocal microscopy and subcellular fractionation of amyloid-expressing 7PA2 cells demonstrated that PSA localizes to the cytoplasm. Therefore, PSA and Aβ are unlikely to be in the same cellular compartment; moreover, when we artificially placed them in the same compartment in flies, we could not detect a direct epistatic interaction. The consequent hypothesis that PSA's suppression of Aβ toxicity is indirect was supported by the finding that Aβ is not a proteolytic substrate for PSA in vitro. Furthermore, we showed that the enzymatic activity of PSA is not required for rescuing Aβ toxicity in neuronal SH-SY5Y cells. We investigated whether the stimulation of autophagy by PSA was responsible for these protective effects. However PSA's promotion of autophagosome fusion with lysosomes required proteolytic activity and so its effect on autophagy is not identical to its protection against Aβ toxicity.
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Registered trials
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