ArticleMolecular psychiatry2022
MEK1/2 inhibition rescues neurodegeneration by TFEB-mediated activation of autophagic lysosomal function in a model of Alzheimer's Disease.
Article in Molecular psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 52 citations in OpenAlex.
- Nuciferine Ameliorates Ovariectomy-Induced Bone Loss via TFEB-Mediated Autophagy-Lysosomal Pathway.Biomolecules · 2026Article
- Selective non-nuclear estrogen receptor activation with PaPE-1 evokes neuroprotection involving mTOR/MEK in an in vitro model of hypoxic/ischemic injury.Pharmacological reports : PR · 2026Article
- Zinc-mediated lysosomal activation by 1H10 enhances autophagy and attenuates tau pathology in Alzheimer's disease models.Molecular brain · 2026Article
- PACS2 Alleviates Sepsis-Induced Myopathy by Activating ERK-MAPK Signalling Pathway to Suppress ER-Phagy.Journal of cachexia, sarcopenia and muscle · 2026Article
- Cytoplasmic retention of IRF3 binding Vimentin competitively with ERK1/2 mitigates acute myeloid leukemia through TFEB nuclear translocation.Cell communication and signaling : CCS · 2026Article
- Chemical and Molecular Strategies in Restoring Autophagic Flux in TDP-43 Proteinopathy.Molecules (Basel, Switzerland) · 2026Review
- Genetic Architecture of Cognitive Resilience in Alzheimer's Disease: Mechanisms, Pathways, and Therapeutic Implications.Neurology international · 2026Review
- Isogenic cortical organoids enable precision targeting of APP variant-specific pathways in Alzheimer's disease.bioRxiv : the preprint server for biology · 2026Article
- eVGeMdb: a manually curated database for experimentally validated genetic modifiers of neurodegenerative disorders.NAR molecular medicine · 2026Article
- Neuroprotective effects ofFrontiers in molecular biosciences · 2026Article
- Metabolites associated with type 2 diabetes and Alzheimer's disease trigger differential intracellular signaling responses in mouse primary neurons.Brain research · 2025Article
- A Proteomics Profiling Reveals the Neuroprotective Effects of Melatonin on Exogenous β-amyloid-42 Induced Mitochondrial Impairment, Intracellular β-amyloid Accumulation and Tau Hyperphosphorylation in Human SH-SY5Y Cells.Cell biology international · 2025Article
- Dihydromyricetin restores lysosomal function in Schwann cells to alleviate bortezomib-induced peripheral neuropathy via ERK/TFEB signaling.Archives of toxicology · 2025Article
- Article
- Experimental and clinical tests of FDA-approved kinase inhibitors for the treatment of neurological disorders (update 2024).Exploration of drug science · 2025Article
- Drug repurposing candidates for amyotrophic lateral sclerosis using common and rare genetic variants.Brain communications · 2025Article
- TRPV1 alleviates APOE4-dependent microglial antigen presentation and T cell infiltration in Alzheimer's disease.Translational neurodegeneration · 2024Article
- Multiomic ALS signatures highlight subclusters and sex differences suggesting the MAPK pathway as therapeutic target.Nature communications · 2024Article
- Interaction of high-fat diet and brain trauma alters adipose tissue macrophages and brain microglia associated with exacerbated cognitive dysfunction.Journal of neuroinflammation · 2024Article
- Epileptic seizures induced by pentylenetetrazole kindling accelerate Alzheimer-like neuropathology in 5×FAD mice.Frontiers in pharmacology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alzheimer's Disease (AD) is a progressive neurodegenerative disorder, which is characterized by cognitive deficit due to synaptic loss and neuronal death. Extracellular amyloid β plaques are one of the pathological hallmarks of AD. The autophagic lysosomal pathway is the essential mechanism to maintain cellular homeostasis by driving clearance of protein aggregates and is dysfunctional in AD. Here, we showed that inhibiting MEK/ERK signaling using a clinically available MEK1/2 inhibitor, trametinib (GSK1120212, SNR1611), induces the protection of neurons through autophagic lysosomal activation mediated by transcription factor EB (TFEB) in a model of AD. Orally administered trametinib recovered impaired neural structures, cognitive functions, and hippocampal long-term potentiation (LTP) in 5XFAD mice. Trametinib also reduced Aβ deposition via induction of autophagic lysosomal activation. RNA-sequencing analysis revealed upregulation of autophagic lysosomal genes by trametinib administration. In addition, trametinib inhibited TFEB phosphorylation at Ser142 and promoted its nuclear translocation, which in turn induced autophagic lysosomal related genes, indicating that trametinib activates the autophagic lysosomal process through TFEB activation. From these observations, we concluded that MEK inhibition provides neuronal protection from the Aβ burden by increasing autophagic lysosomal activity. Thus, MEK inhibition may be an effective therapeutic strategy for AD.
Indexed as
Identifiers
What OpenQuestion holds
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.