ArticleThe Journal of biological chemistry2022
Ammonia induces amyloidogenesis in astrocytes by promoting amyloid precursor protein translocation into the endoplasmic reticulum.
Article in The Journal of biological chemistry, 2022. 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, 15 citations in OpenAlex.
- Effect of Ammonia onAntioxidants (Basel, Switzerland) · 2026Article
- Network Pharmacology and Experimental Validation Unravel How Puerarin Improves Chronic Postoperative Pain.Molecular biotechnology · 2026Article
- Associations of PMThe Journal of international medical research · 2026Article
- Ammonia reduces glutamine synthetase expression in astrocytes via activation of Hippo-YAP signaling pathways.Communications biology · 2025Article
- Soil to Synapse: Molecular Insights into the Neurotoxicity of Common Gardening Chemicals in Alzheimer's and Parkinson's Disease.International journal of molecular sciences · 2025Review
- Low extracellular pH protects cancer cells from ammonia toxicity.Cell death discovery · 2025Article
- Alzheimer's Disease: Models and Molecular Mechanisms Informing Disease and Treatments.Bioengineering (Basel, Switzerland) · 2024Review
- Amyloid precursor protein induces reactive astrogliosis.bioRxiv : the preprint server for biology · 2023Article
- Dysregulated cellular redox status during hyperammonemia causes mitochondrial dysfunction and senescence by inhibiting sirtuin-mediated deacetylation.Aging cell · 2023Article
- Ferroptosis: a new regulatory mechanism in neuropathic pain.Frontiers in aging neuroscience · 2023Review
- New Insight Into Mechanisms of Hepatic Encephalopathy: An Integrative Analysis Approach to Identify Molecular Markers and Therapeutic Targets.Bioinformatics and biology insights · 2023Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hyperammonemia is known to cause various neurological dysfunctions such as seizures and cognitive impairment. Several studies have suggested that hyperammonemia may also be linked to the development of Alzheimer's disease (AD). However, the direct evidence for a role of ammonia in the pathophysiology of AD remains to be discovered. Herein, we report that hyperammonemia increases the amount of mature amyloid precursor protein (mAPP) in astrocytes, the largest and most prevalent type of glial cells in the central nervous system that are capable of metabolizing glutamate and ammonia, and promotes amyloid beta (Aβ) production. We demonstrate the accumulation of mAPP in astrocytes was primarily due to enhanced endocytosis of mAPP from the plasma membrane. A large proportion of internalized mAPP was targeted not to the lysosome, but to the endoplasmic reticulum, where processing enzymes β-secretase BACE1 (beta-site APP cleaving enzyme 1) and γ-secretase presenilin-1 are expressed, and mAPP is cleaved to produce Aβ. Finally, we show the ammonia-induced production of Aβ in astrocytic endoplasmic reticulum was specific to Aβ42, a principal component of senile plaques in AD patients. Our studies uncover a novel mechanism of Aβ42 production in astrocytes and also provide the first evidence that ammonia induces the pathogenesis of AD by regulating astrocyte function.
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