ArticleNature structural & molecular biology2022
Tau modification by the norepinephrine metabolite DOPEGAL stimulates its pathology and propagation.
Article in Nature structural & molecular biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 46 citations in OpenAlex.
- A new hope: locus coeruleus-norepinephrine system at the nexus of neuropsychiatric symptoms.Molecular psychiatry · 2026Review
- The Oral-Brain Axis: A Unified Framework Linking Trigeminal Sensorimotor Dysfunction, Chronic Stress, Neuroinflammation, and Neurodegeneration.International journal of molecular sciences · 2026Review
- A metabolite extracted from Escherichia coli suppresses tau aggregation.The Biochemical journal · 2026Article
- Preclinical Catecholaminergic Biomarkers of Central Lewy Body Diseases.Journal of clinical neurology (Seoul, Korea) · 2026Review
- The delta-opioid receptor: a therapeutic target for Alzheimer's disease.Frontiers in aging neuroscience · 2026Review
- Tau protein: Physiological functions and multifaceted roles in neurodegenerative and psychiatric disorders.Genomic psychiatry : advancing science from genes to society · 2025Article
- Therapeutic strategies based on macrophages and their derivatives: Targeted drug delivery platforms and disease treatment.Journal of pharmaceutical analysis · 2025Review
- Long-term Locus Coeruleus Stimulation Exacerbates Tau Pathology in PS19 Mice.bioRxiv : the preprint server for biology · 2025Article
- The rhythm of decline: Circadian disruption in neurodegeneration.Journal of food and drug analysis · 2025Review
- Alcohol consumption during early adulthood increases the vulnerability of locus coeruleus neurons and amyloid beta pathology in female APP/PS1 mice.Alcohol (Fayetteville, N.Y.) · 2025Article
- Not 'Inactive' After All: Cardiotoxic Mechanisms of Catecholamine Metabolism by Monoamine Oxidase.Cardiovascular toxicology · 2025Review
- Immunotherapy against tau fragment diminishes AD pathology, improving synaptic function and cognition.Molecular neurodegeneration · 2025Article
- Astaxanthin Mitigates ADHD Symptoms in Spontaneously Hypertensive Rats via Dopaminergic Modulation and Brain-Gut Axis Regulation.Molecules (Basel, Switzerland) · 2025Article
- Tyrosinase-induced neuromelanin accumulation triggers rapid dysregulation and degeneration of the mouse locus coeruleus.bioRxiv : the preprint server for biology · 2025Article
- A Focus on the Link Between Metal Dyshomeostasis, Norepinephrine, and Protein Aggregation.Antioxidants (Basel, Switzerland) · 2025Review
- ApoE3 R136S binds to Tau and blocks its propagation, suppressing neurodegeneration in mice with Alzheimer's disease.Neuron · 2025Article
- Long-term exposure to excessive norepinephrine in the brain induces tau aggregation, neuronal death, and cognitive deficits in early tau transgenic mice.Aging cell · 2025Article
- Fading Blue: Exploring the Causes of Locus Coeruleus Damage Across the Lifespan.Antioxidants (Basel, Switzerland) · 2025Review
- Noradrenergic therapies in neurodegenerative disease: from symptomatic to disease modifying therapy?Brain communications · 2025Review
- The Neuroanatomy of Induced Pluripotent Stem Cells: In Vitro Models of Subcortical Nuclei in Neurodegenerative Disorders.Current issues in molecular biology · 2024Review
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
The noradrenergic locus ceruleus (LC) is the first site of detectable tau pathology in Alzheimer's disease (AD), but the mechanisms underlying the selective vulnerability of the LC in AD have not been completely identified. In the present study, we show that DOPEGAL, a monoamine oxidase A (MAO-A) metabolite of norepinephrine (NE), reacts directly with the primary amine on the Lys353 residue of tau to stimulate its aggregation and facilitate its propagation. Inhibition of MAO-A or mutation of the Lys353 residue to arginine (Lys353Arg) decreases tau Lys353-DOPEGAL levels and diminishes tau pathology spreading. Wild-type tau preformed fibrils (PFFs) trigger Lys353-DOPEGAL formation, tau pathology propagation and cognitive impairment in MAPT transgenic mice, all of which are attenuated with PFFs made from the Lys353Arg mutant. Thus, the selective vulnerability of LC neurons in AD may be explained, in part, by NE oxidation via MAO-A into DOPEGAL, which covalently modifies tau and accelerates its aggregation, toxicity and propagation.
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