ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009
Proneurotrophin-3 is a neuronal apoptotic ligand: evidence for retrograde-directed cell killing.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Finding memo: versatile interactions of the VPS10p-Domain receptors in Alzheimer's disease.Molecular neurodegeneration · 2022Pooled it
- Contribution of proneurotrophin-3 to nerve trauma-induced neuropathic pain through promoting TrkC-mediated increase of CCL2 in primary sensory neurons.Brain, behavior, and immunity · 2026Article
- The Potential Role of Auditory Nerve Development in Sensorineural Hearing Loss: from Pathophysiology to Treatment Insights.International journal of medical sciences · 2026Review
- Proneurotrophin-3 contributes to chemotherapy-induced neuropathic pain through TrkC-mediated CCL2 elevation in DRG neurons.EMBO reports · 2025Article
- Microfluidic Cultures of Basal Forebrain Cholinergic Neurons for Assessing Retrograde Cell Death by Live Imaging.Bio-protocol · 2025Article
- Cortical Brain Injury Causes Retrograde Degeneration of Afferent Basal Forebrain Cholinergic Neurons via the p75NTR.eNeuro · 2023Article
- Article
- Decellularized peripheral nerve as an injectable delivery vehicle for neural applications.Journal of biomedical materials research. Part A · 2022Article
- A combined evolutionary and structural approach to disclose the primary structural determinants essential for proneurotrophins biological functions.Computational and structural biotechnology journal · 2021Article
- c-Jun N-terminal kinase (JNK)-dependent internalization and Rab5-dependent endocytic sorting mediate long-distance retrograde neuronal death induced by axonal BDNF-p75 signaling.Scientific reports · 2019Article
- The role of neurotrophins in psychopathology and cardiovascular diseases: psychosomatic connections.Journal of neural transmission (Vienna, Austria : 1996) · 2019Review
- Retrograde Degenerative Signaling Mediated by the p75 Neurotrophin Receptor Requires p150Developmental cell · 2018Article
- PROneurotrophins and CONSequences.Molecular neurobiology · 2018Review
- Neurotrophin Signaling and Stem Cells-Implications for Neurodegenerative Diseases and Stem Cell Therapy.Molecular neurobiology · 2017Review
- Retrograde apoptotic signaling by the p75 neurotrophin receptor.Neuronal signaling · 2017Review
- Neurotrophin signalling: novel insights into mechanisms and pathophysiology.Clinical science (London, England : 1979) · 2017Review
- Effects of striatal transplantation of cells transfected with GDNF gene without pre- and pro-regions in mouse model of Parkinson's disease.BMC neuroscience · 2016Article
- Layer 2/3 pyramidal cells in the medial prefrontal cortex moderate stress induced depressive behaviors.eLife · 2015Article
- Establishing a cellular FRET-based fluorescence plate reader assay to monitor proNGF-induced cross-linking of sortilin and the neurotrophin receptor p75(NTR).International journal of biochemistry and molecular biology · 2015Article
- The proform of glia cell line-derived neurotrophic factor: a potentially biologically active protein.Molecular neurobiology · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Although mature neurotrophins are well described trophic factors that elicit retrograde survival signaling, the precursor forms of neurotrophins (i.e., proneurotrophins) can function as high-affinity apoptotic ligands for selected neural populations. An outstanding question is whether target-derived proneurotrophins might affect neuronal survival/death decisions through a retrograde transport mechanism. Since neurotrophin-3 (NT-3) is highly expressed in non-neural tissues that receive peripheral innervation, we investigated the localized actions of its precursor (proNT-3) on sympathetic neurons in the present study. Pharmacological inhibition of intracellular furin proteinase activity in 293T cells resulted in proNT-3 release instead of mature NT-3, whereas membrane depolarization in cerebellar granule neurons stimulated endogenous proNT-3 secretion, suggesting that proNT-3 is an inducible bona fide ligand in the nervous system. Our data also indicate that recombinant proNT-3 induced sympathetic neuron death that is p75(NTR)- and sortilin-dependent, with hallmark features of apoptosis including JNK (c-Jun N-terminal kinase) activation and nuclear fragmentation. Using compartmentalized culture systems that segregate neuronal cell bodies from axons, proNT-3, acting within the distal axon compartment, elicited sympathetic neuron death and overrode the survival-promoting actions of NGF. Together, these results raise the intriguing possibility that dysregulation of proneurotrophin processing/release by innervated targets can be deleterious to the neurons projecting to these sites.
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.