ArticleJournal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology2012
Anti-inflammatory effects of ladostigil and its metabolites in aged rat brain and in microglial cells.
Article in Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- Low-dose ladostigil for mild cognitive impairment: A phase 2 placebo-controlled clinical trial.Neurology · 2019Trial
- Unveiling Neuroprotective Potential in Tempeh Peptide Extracts byReports of biochemistry & molecular biology · 2025Article
- Article
- Therapeutic agents for Alzheimer's disease: a critical appraisal.Frontiers in aging neuroscience · 2024Review
- Coordinated Transcriptional Waves Define the Inflammatory Response of Primary Microglial Culture.International journal of molecular sciences · 2023Article
- Oxidative Stress and Its Modulation by Ladostigil Alter the Expression of Abundant Long Non-Coding RNAs in SH-SY5Y Cells.Non-coding RNA · 2022Article
- Ladostigil Attenuates Induced Oxidative Stress in Human Neuroblast-like SH-SY5Y Cells.Biomedicines · 2021Article
- Monoamine Oxidase Inhibitors: A Review of Their Anti-Inflammatory Therapeutic Potential and Mechanisms of Action.Frontiers in pharmacology · 2021Review
- Monoamine Oxidase Inhibitors: From Classic to New Clinical Approaches.Handbook of experimental pharmacology · 2021Review
- Monoamine Oxidase-B Inhibitor Reduction in Pro-Inflammatory Cytokines Mediated by Inhibition of cAMP-PKA/EPAC Signaling.Frontiers in pharmacology · 2021Article
- Age-Induced Spatial Memory Deficits in Rats Are Correlated with Specific Brain Region Alterations in Microglial Morphology and Gene Expression.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2019Article
- Design, synthesis and evaluation of indole derivatives as multifunctional agents against Alzheimer's disease.MedChemComm · 2018Article
- Neuroprotective effects of multifaceted hybrid agents targeting MAO, cholinesterase, iron and β-amyloid in ageing and Alzheimer's disease.British journal of pharmacology · 2016Review
- Neuroprotective and neurorestorative potential of propargylamine derivatives in ageing: focus on mitochondrial targets.Journal of neural transmission (Vienna, Austria : 1996) · 2016Review
- M30 Antagonizes Indoleamine 2,3-Dioxygenase Activation and Neurodegeneration Induced by Corticosterone in the Hippocampus.PloS one · 2016Article
- Dose-dependent effects of ladostigil on microglial activation and cognition in aged rats.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2013Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Impaired mitochondrial function accompanied by microglial activation and the release of nitric oxide (NO) and pro-inflammatory cytokines has been reported in Alzheimer's disease, its prodromal phase of Mild Cognitive Impairment (MCI) and in aged rats. The present study showed that 6 months treatment of 16 month old rats with ladostigil (1 mg/kg/day), a novel drug designed for the treatment of MCI, prevented the development of spatial memory deficits at 22 months of age and significantly decreased the gene expression of IL-1β, IL-6, TNF-α and inducible nitric oxide synthase (iNOS) in the parietal cortex. It was also shown that concentrations ranging from 1nM-1 μM of ladostigil and three of its active metabolites inhibited the release of nitric oxide (NO) induced by lipopolysaccharide (LPS) from mouse microglial cells by up to 35-40 %. Ladostigil and its metabolites (10nM) also reduced TNF-α mRNA and protein by 25-35 % and IL-1β and inducible nitric oxide synthase (iNOS) mRNA by 20-35 %. The concentration of 10nM is in the range of that of the parent drug, R-MCPAI and R-HPAI found in plasma after oral administration of ladostigil (1 mg/kg/day) to rats. All the compounds inhibited the degradation of IkB-α and nuclear translocation of the p65 subunit of NF-kB. They also inhibited phosphorylation of p38 and ERK1/2 mitogen-activated protein kinase (MAPK), but had no effect on that of JNK. We propose that the anti-inflammatory activity may contribute towards the neuroprotective action of ladostigil against the development of memory impairments induced by aging or toxin-induced microglial activation.
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