ArticleNature communications2020
Retromer stabilization results in neuroprotection in a model of Amyotrophic Lateral Sclerosis.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 74 citations in OpenAlex.
- Retromer-targeted therapy for neurodegenerative diseases.Molecular neurodegeneration · 2026Review
- Monovalent Nondegrading Molecular Glues: An Updated Overview of Emerging Mechanisms and Therapeutic Development.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Astrocytic VPS35 coordinates iron homeostasis with HIF1α-VEGFa signaling to prevent astrocytic ferroptosis and to promote neocortical angiogenesis.Cell & bioscience · 2026Article
- Synaptojanin1 regulates synaptic dopamine release and axonal integrity via retromer-dependent endosomal sorting.Research square · 2026Article
- RhoGEF12 regulates endosomal SORL1-retromer and its inhibition is therapeutic in human neuronal models of Alzheimer's disease.bioRxiv : the preprint server for biology · 2026Article
- A role for the cholinergic neuron circadian clock in RNA metabolism and mediating neurodegeneration.Life science alliance · 2026Article
- TDP-43-mediated alternative polyadenylation is associated with a reduction in VPS35 and VPS29 expression in frontotemporal dementia.PLoS biology · 2026Article
- Aryl Guanyl Hydrazones: A Viable Strategy for Designing BBB-Permeable, Neuroactive Compounds?ACS chemical neuroscience · 2025Review
- Seasonal and comparative evidence of adaptive gene expression in mammalian brain size plasticity.eLife · 2025Article
- Molecular basis for the assembly of the Vps5-Vps17 SNX-BAR proteins with Retromer.Nature communications · 2025Article
- VPS35-Retromer: Multifunctional Roles in Various Biological Processes - A Focus on Neurodegenerative Diseases and Cancer.Journal of inflammation research · 2025Review
- Endosomal traffic disorders: a driving force behind neurodegenerative diseases.Translational neurodegeneration · 2024Review
- Stabilization of the retromer complex: Analysis of novel binding sites of bis-1,3-phenyl guanylhydrazone 2a to the VPS29/VPS35 interface.Computational and structural biotechnology journal · 2024Article
- VPS35 or retromer as a potential target for neurodegenerative disorders: barriers to progress.Expert opinion on therapeutic targets · 2024Review
- Update on recent advances in amyotrophic lateral sclerosis.Journal of neurology · 2024Review
- Dysregulation of SNX1-retromer axis in pharmacogenetic models of Parkinson's disease.Cell death discovery · 2024Article
- TDP-43-stratified single-cell proteomics of postmortem human spinal motor neurons reveals protein dynamics in amyotrophic lateral sclerosis.Cell reports · 2024Article
- Pharmacologic enhancement of retromer rescues endosomal pathology induced by defects in the Alzheimer's gene SORL1.Stem cell reports · 2023Article
- VPS35 and α-Synuclein fail to interact to modulate neurodegeneration in rodent models of Parkinson's disease.Molecular neurodegeneration · 2023Article
- Multi-omic approach characterises the neuroprotective role of retromer in regulating lysosomal health.Nature communications · 2023Article
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Amyotrophic Lateral Sclerosis (ALS) is a fatal disease characterized by the degeneration of upper and lower motor neurons (MNs). We find a significant reduction of the retromer complex subunit VPS35 in iPSCs-derived MNs from ALS patients, in MNs from ALS post mortem explants and in MNs from SOD1G93A mice. Being the retromer involved in trafficking of hydrolases, a pathological hallmark in ALS, we design, synthesize and characterize an array of retromer stabilizers based on bis-guanylhydrazones connected by a 1,3-phenyl ring linker. We select compound 2a as a potent and bioavailable interactor of VPS35-VPS29. Indeed, while increasing retromer stability in ALS mice, compound 2a attenuates locomotion impairment and increases MNs survival. Moreover, compound 2a increases VPS35 in iPSCs-derived MNs and shows brain bioavailability. Our results clearly suggest the retromer as a valuable druggable target in ALS.
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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.