ArticleHuman molecular genetics2016
A small molecule p75NTR ligand normalizes signalling and reduces Huntington's disease phenotypes in R6/2 and BACHD mice.
Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 46 citations in OpenAlex.
- Molecular neurobiological insights on integrative role of Trk neurotrophic receptors and their small-molecule agonists in neurodegenerative conditions.Experimental brain research · 2026Review
- Taming the "death receptor": translating the first-in-class p75Journal of translational medicine · 2026Review
- Molecular mechanisms of autophagy-lysosomal pathway dysfunction in neurodegenerative diseases and therapeutic strategies for lysosomal repair: a review.Frontiers in neuroscience · 2026Review
- p75NTR Modulation by LM11A-31 Counteracts Oxidative Stress and Cholesterol Dysmetabolism in a Rotenone-Induced Cell Model of Parkinson's Disease.Neurochemical research · 2025Article
- Small molecule modulation of p75Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Oxidative Stress Suppresses Trk Signaling While Stimulating JNK-Mediated Endocytosis and Cleavage of p75Journal of neurochemistry · 2025Article
- Brain-Derived Neurotrophic Factor (BDNF) in Huntington's Disease: Neurobiology and Therapeutic Potential.Current neuropharmacology · 2025Review
- Modulation of p75 neurotrophin receptor mitigates brain damage following ischemic stroke in mice.Neural regeneration research · 2024Article
- Genetic and Pharmacological Modulation of P75 Neurotrophin Receptor Attenuate Brain Damage After Ischemic Stroke in Mice.Molecular neurobiology · 2024Article
- Adjunctive treatments for pneumococcal meningitis: a systematic review of experimental animal models.Brain communications · 2024Review
- Brain-Derived Neurotrophic Factor Dysregulation as an Essential Pathological Feature in Huntington's Disease: Mechanisms and Potential Therapeutics.Biomedicines · 2023Review
- IntelliCage: the development and perspectives of a mouse- and user-friendly automated behavioral test system.Frontiers in behavioral neuroscience · 2023Review
- To re-examine the intersection of microglial activation and neuroinflammation in neurodegenerative diseases from the perspective of pyroptosis.Frontiers in aging neuroscience · 2023Review
- Suppression of HIV-associated Macrophage Activation by a p75 Neurotrophin Receptor Ligand.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2022Article
- RhoA Signaling in Neurodegenerative Diseases.Cells · 2022Review
- NGF Modulates Cholesterol Metabolism and Stimulates ApoE Secretion in Glial Cells Conferring Neuroprotection against Oxidative Stress.International journal of molecular sciences · 2022Article
- Post-Stroke Administration of the p75 Neurotrophin Receptor Modulator, LM11A-31, Attenuates Chronic Changes in Brain Metabolism, Increases Neurotransmitter Levels, and Improves Recovery.The Journal of pharmacology and experimental therapeutics · 2022Article
- Regulation of the p75 neurotrophin receptor attenuates neuroinflammation and stimulates hippocampal neurogenesis in experimental Streptococcus pneumoniae meningitis.Journal of neuroinflammation · 2021Article
- In vivo functions of p75Trends in pharmacological sciences · 2021Review
- Neuroimaging, Urinary, and Plasma Biomarkers of Treatment Response in Huntington's Disease: Preclinical Evidence with the p75Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Decreases in the ratio of neurotrophic versus neurodegenerative signalling play a critical role in Huntington’s disease (HD) pathogenesis and recent evidence suggests that the p75 neurotrophin receptor (NTR) contributes significantly to disease progression. p75NTR signalling intermediates substantially overlap with those promoting neuronal survival and synapse integrity and with those affected by the mutant huntingtin (muHtt) protein. MuHtt increases p75NTR-associated deleterious signalling and decreases survival signalling suggesting that p75NTR could be a valuable therapeutic target. This hypothesis was investigated by examining the effects of an orally bioavailable, small molecule p75NTR ligand, LM11A-31, on HD-related neuropathology in HD mouse models (R6/2, BACHD). LM11A-31 restored striatal AKT and other pro-survival signalling while inhibiting c-Jun kinase (JNK) and other degenerative signalling. Normalizing p75NTR signalling with LM11A-31 was accompanied by reduced Htt aggregates and striatal cholinergic interneuron degeneration as well as extended survival in R6/2 mice. The p75NTR ligand also decreased inflammation, increased striatal and hippocampal dendritic spine density, and improved motor performance and cognition in R6/2 and BACHD mice. These results support small molecule modulation of p75NTR as an effective HD therapeutic strategy. LM11A-31 has successfully completed Phase I safety and pharmacokinetic clinical trials and is therefore a viable candidate for clinical studies in HD.
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Registered trials
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