ArticleNeurobiology of disease2017
Nortriptyline inhibits aggregation and neurotoxicity of alpha-synuclein by enhancing reconfiguration of the monomeric form.
Article in Neurobiology of disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
- Placebo-controlled three-armed pilot trial of Escitalopram or Nortriptyline for depressive symptoms in Parkinson's disease (ADepT-PD).Journal of neural transmission (Vienna, Austria : 1996) · 2026Trial
- Exploring the association between antidepressants, progression and mortality in Huntington's disease.Brain : a journal of neurology · 2026Article
- Lipid membrane remodeling by myristic acid treatment reverses Parkinson's disease α-synuclein phenotypes in patient neurons.npj metabolic health and disease · 2026Article
- Synergistic Effects of Levodopa, Benserazide, and Nortriptyline on Behavioral Impairments and Brain Pathology in an Experimental Rat Model of Parkinson's Disease.Neurology research international · 2026Article
- A Review of the Recent Advances in the Pharmacological Management of Parkinson's Disease.Cureus · 2025Review
- Chronic stress induces depression-like behaviors and Parkinsonism via upregulating α-synuclein.NPJ Parkinson's disease · 2025Article
- Article
- O-GlcNAc Modification of α-Synuclein Can Alter Monomer Dynamics to Control Aggregation Kinetics.ACS chemical neuroscience · 2024Article
- Article
- Lipase regulation of cellular fatty acid homeostasis as a Parkinson's disease therapeutic strategy.NPJ Parkinson's disease · 2022Article
- Vesicle trafficking and lipid metabolism in synucleinopathy.Acta neuropathologica · 2021Review
- Parkinson's disease and the gastrointestinal microbiome.Journal of neurology · 2020Review
- Rapid Alpha-Synuclein Toxicity in a Neural Cell Model and Its Rescue by a Stearoyl-CoA Desaturase Inhibitor.International journal of molecular sciences · 2020Article
- Soluble endogenous oligomeric α-synuclein species in neurodegenerative diseases: Expression, spreading, and cross-talk.Journal of Parkinson's disease · 2020Review
- Dynamic behaviors of α-synuclein and tau in the cellular context: New mechanistic insights and therapeutic opportunities in neurodegeneration.Neurobiology of disease · 2019Review
- Cell models of lipid-rich α-synuclein aggregation validate known modifiers of α-synuclein biology and identify stearoyl-CoA desaturase.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Polypharmacy in Parkinson's disease: risks and benefits with little evidence.Journal of neural transmission (Vienna, Austria : 1996) · 2019Article
- Pre-structured hydrophobic peptide β-strands: A universal amyloid trap?Archives of biochemistry and biophysics · 2019Review
- Lipidomic Analysis of α-Synuclein Neurotoxicity Identifies Stearoyl CoA Desaturase as a Target for Parkinson Treatment.Molecular cell · 2019Article
- Cyclized NDGA modifies dynamic α-synuclein monomers preventing aggregation and toxicity.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
18 authors at 9 institutions in 2 countries.
Funding
Abstract
The pathology of Parkinson's disease and other synucleinopathies is characterized by the formation of intracellular inclusions comprised primarily of misfolded, fibrillar α-synuclein (α-syn). One strategy to slow disease progression is to prevent the misfolding and aggregation of its native monomeric form. Here we present findings that support the contention that the tricyclic antidepressant compound nortriptyline (NOR) has disease-modifying potential for synucleinopathies. Findings from in vitro aggregation and kinetics assays support the view that NOR inhibits aggregation of α-syn by directly binding to the soluble, monomeric form, and by enhancing reconfiguration of the monomer, inhibits formation of toxic conformations of the protein. We go on to demonstrate that NOR inhibits the accumulation, aggregation and neurotoxicity of α-syn in multiple cell and animal models. These findings suggest that NOR, a compound with established safety and efficacy for treatment of depression, may slow progression of α-syn pathology by directly binding to soluble, native, α-syn, thereby inhibiting pathological aggregation and preserving its normal functions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.