ArticleProceedings of the National Academy of Sciences of the United States of America2013
Tissue plasminogen activator regulates Purkinje neuron development and survival.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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
22 citing papers in PubMed, 41 citations in OpenAlex.
- Cell replacement in the degenerating cerebellum: a historical essay of discovery.Journal of neurology · 2025Review
- Impaired Aggrephagy, Interrupted Vesicular Trafficking, and Cellular Stress, Lead to Protein Aggregation, and Synaptic Dysfunction in Cerebellum of Children and Adults with Idiopathic Autism.Cerebellum (London, England) · 2025Article
- BDNF and Cerebellar Ataxia.Current drug research reviews · 2024Review
- Transcriptomic Analyses of Neurotoxic Astrocytes Derived from Adult Triple Transgenic Alzheimer's Disease Mice.Journal of molecular neuroscience : MN · 2023Article
- Astrocyte tissue plasminogen activator expression during brain development and its role in pyramidal neuron neurite outgrowth.Neuroscience letters · 2022Article
- Dissolution Effect of Alteplase on Arterial Blood Clot Model of Hypertensive Intracerebral Hemorrhage PatientsFrontiers in neurology · 2022Article
- α2-Antiplasmin as a potential regulator of the spatial memory process and age-related cognitive decline.Molecular brain · 2020Article
- Nna1 gene deficiency triggers Purkinje neuron death by tubulin hyperglutamylation and ER dysfunction.JCI insight · 2020Article
- ADCK4 Deficiency Destabilizes the Coenzyme Q Complex, Which Is Rescued by 2,4-Dihydroxybenzoic Acid Treatment.Journal of the American Society of Nephrology : JASN · 2020Article
- Plasminogen activator system homeostasis and its dysregulation by ethanol in astrocyte cultures and the developing brain.Neuropharmacology · 2018Article
- Synaptic aging disrupts synaptic morphology and function in cerebellar Purkinje cells.Neural regeneration research · 2018Article
- Chronic inflammation and apoptosis propagate in ischemic cerebellum and heart of non-human primates.Oncotarget · 2017Article
- tPA Modulation of the Blood-Brain Barrier: A Unifying Explanation for the Pleiotropic Effects of tPA in the CNS.Seminars in thrombosis and hemostasis · 2017Review
- Tissue Plasminogen Activator Expression Is Restricted to Subsets of Excitatory Pyramidal Glutamatergic Neurons.Molecular neurobiology · 2016Article
- Experimental neurotransplantation treatment for hereditary cerebellar ataxias.Cerebellum & ataxias · 2016Review
- Identification of a neurovascular signaling pathway regulating seizures in mice.Annals of clinical and translational neurology · 2015Article
- tPA Deficiency in Mice Leads to Rearrangement in the Cerebrovascular Tree and Cerebroventricular Malformations.Frontiers in cellular neuroscience · 2015Article
- Impacts of tissue-type plasminogen activator (tPA) on neuronal survival.Frontiers in cellular neuroscience · 2015Review
- Tissue-type plasminogen activator is a neuroprotectant in the central nervous system.Frontiers in cellular neuroscience · 2015Review
- From mice to men: lessons from mutant ataxic mice.Cerebellum & ataxias · 2014Review
Corrections and comments
- Commented on by
Authors and funding
8 authors at 7 institutions in 2 countries.
Funding
Abstract
The cerebellar cortex is centrally involved in motor coordination and learning, and its sole output is provided by Purkinje neurons (PNs). Growth of PN dendrites and their major synaptic input from granule cell parallel fiber axons takes place almost entirely in the first several postnatal weeks. PNs are more vulnerable to cell death than most other neurons, but the mechanisms remain unclear. We find that the homozygous nervous (nr) mutant mouse's 10-fold-increased cerebellar tissue plasminogen activator (tPA), a part of the tPA/plasmin proteolytic system, influences several different molecular mechanisms, each regulating a key aspect of postnatal PN development, followed by selective PN necrosis, as follows. (i) Excess endogenous or exogenous tPA inhibits dendritic growth in vivo and in vitro by activating protein kinase Cγ and phosphorylation of microtubule-associated protein 2. (ii) tPA/plasmin proteolysis impairs parallel fiber-PN synaptogenesis by blocking brain-derived neurotrophic factor/tyrosine kinase receptor B signaling. (iii) Voltage-dependent anion channel 1 (a mitochondrial and plasma membrane protein) bound with kringle 5 (a peptide derived from the excess plasminogen) promotes pathological enlargement and rounding of PN mitochondria, reduces mitochondrial membrane potential, and damages plasma membranes. These abnormalities culminate in young nr PN necrosis that can be mimicked in wild-type PNs by exogenous tPA injection into cerebellum or prevented by endogenous tPA deletion in nr:tPA-knockout double mutants. In sum, excess tPA/plasmin, through separate downstream molecular mechanisms, regulates postnatal PN dendritogenesis, synaptogenesis, mitochondrial structure and function, and selective PN viability.
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.