ArticleCell death and differentiation2020
Coupling of terminal differentiation deficit with neurodegenerative pathology in Vps35-deficient pyramidal neurons.
Article in Cell death and differentiation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 47 citations in OpenAlex.
- Retromer-targeted therapy for neurodegenerative diseases.Molecular neurodegeneration · 2026Review
- Late Endosome Transport by RILP-RAB7A Promotes Dendrite Arborization Independently of Degradation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Astrocytic VPS35 coordinates iron homeostasis with HIF1α-VEGFa signaling to prevent astrocytic ferroptosis and to promote neocortical angiogenesis.Cell & bioscience · 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
- Neuronal MCT2 promotes angiogenesis via lactate in the developing mouse neocortex.Cell death and differentiation · 2026Article
- Adenylyl Cyclase 8 in Dorsal CA1 Neurons Prevents Depressive-Like Behaviors by Maintaining Neuronal Excitability and Glutamatergic Neurotransmission Through TIP39-PTH2R Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- TDP-43-mediated alternative polyadenylation is associated with a reduction in VPS35 and VPS29 expression in frontotemporal dementia.PLoS biology · 2026Article
- Late endosome transport by RILP-RAB7A promotes dendrite arborization.bioRxiv : the preprint server for biology · 2025Article
- VPS35 or retromer as a potential target for neurodegenerative disorders: barriers to progress.Expert opinion on therapeutic targets · 2024Review
- VPS35 and retromer dysfunction in Parkinson's disease.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- TDP-43-stratified single-cell proteomics of postmortem human spinal motor neurons reveals protein dynamics in amyotrophic lateral sclerosis.Cell reports · 2024Article
- TMEM106B core deposition associates with TDP-43 pathology and is increased in risk SNP carriers for frontotemporal dementia.Science translational medicine · 2024Article
- Multi-omic approach characterises the neuroprotective role of retromer in regulating lysosomal health.Nature communications · 2023Article
- Neuroinflammation and Parkinson's Disease-From Neurodegeneration to Therapeutic Opportunities.Cells · 2022Review
- Understanding the contributions of VPS35 and the retromer in neurodegenerative disease.Neurobiology of disease · 2022Review
- Critical Role of Neuronal Vps35 in Blood Vessel Branching and Maturation in Developing Mouse Brain.Biomedicines · 2022Article
- Microglial VPS35 deficiency impairs Aβ phagocytosis and Aβ-induced disease-associated microglia, and enhances Aβ associated pathology.Journal of neuroinflammation · 2022Article
- The understudied links of the retromer complex to age-related pathways.GeroScience · 2022Article
- NADPH Oxidase: a Possible Therapeutic Target for Cognitive Impairment in Experimental Cerebral Malaria.Molecular neurobiology · 2022Article
- Identification of the molecular subgroups in Alzheimer's disease by transcriptomic data.Frontiers in neurology · 2022Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Vps35 (vacuolar protein sorting 35) is a key component of retromer that regulates transmembrane protein trafficking. Dysfunctional Vps35 is a risk factor for neurodegenerative diseases, including Parkinson's and Alzheimer's diseases. Vps35 is highly expressed in developing pyramidal neurons, and its physiological role in developing neurons remains to be explored. Here, we provide evidence that Vps35 in embryonic neurons is necessary for axonal and dendritic terminal differentiation. Loss of Vps35 in embryonic neurons results in not only terminal differentiation deficits, but also neurodegenerative pathology, such as cortical brain atrophy and reactive glial responses. The atrophy of neocortex appears to be in association with increases in neuronal death, autophagosome proteins (LC3-II and P62), and neurodegeneration associated proteins (TDP43 and ubiquitin-conjugated proteins). Further studies reveal an increase of retromer cargo protein, sortilin1 (Sort1), in lysosomes of Vps35-KO neurons, and lysosomal dysfunction. Suppression of Sort1 diminishes Vps35-KO-induced dendritic defects. Expression of lysosomal Sort1 recapitulates Vps35-KO-induced phenotypes. Together, these results demonstrate embryonic neuronal Vps35's function in terminal axonal and dendritic differentiation, reveal an association of terminal differentiation deficit with neurodegenerative pathology, and uncover an important lysosomal contribution to both events.
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