ArticleProceedings of the National Academy of Sciences of the United States of America1993
Widespread activation of calcium-activated neutral proteinase (calpain) in the brain in Alzheimer disease: a potential molecular basis for neuronal degeneration.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1993. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 190 papers.
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Who cites it
190 citing papers in PubMed, 580 citations in OpenAlex.
- Environmental Factors Drive Neurodegenerative Diseases Through Glutamate Excitotoxicity: A Convergent Mechanistic Pathway.Neuroscience bulletin · 2026Review
- Investigating the pathogenic role of calpain proteases and the therapeutic potential of their inhibition in mice modelling Machado-Joseph disease.Human molecular genetics · 2026Article
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- Using fibre photometry with a fluorescence resonance energy transfer-based biosensor to test efficacy of calpain inhibitorsBrain communications · 2026Article
- PHLPP1 deficiency alleviates dopaminergic neurodegeneration and represses neuroinflammation in Parkinson's disease.Behavioral and brain functions : BBF · 2025Article
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- Cannabidiol and Alzheimer Disease: A Comprehensive Review and In Silico Insights Into Molecular Interactions.The European journal of neuroscience · 2025Review
- Polymers for the treatment of Alzheimer's disease.Frontiers in pharmacology · 2025Review
- Dysregulated calcium signaling in the aged primate association cortices: vulnerability to Alzheimer's disease neuropathology.Frontiers in aging neuroscience · 2025Review
- Critical role of alpha spectrin in DNA repair: the importance of μ-calpain and Fanconi anemia proteins.Experimental biology and medicine (Maywood, N.J.) · 2025Review
- Nanoscale imaging of pT217-tau in aged rhesus macaque entorhinal and dorsolateral prefrontal cortex: Evidence of interneuronal trafficking and early-stage neurodegeneration.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- A microtubule stabilizer ameliorates protein pathogenesis and neurodegeneration in mouse models of repetitive traumatic brain injury.Science translational medicine · 2023Article
- Heart failure-induced cognitive dysfunction is mediated by intracellular CaNature neuroscience · 2023Article
- Calpain activity is negatively regulated by a KCTD7-Cullin-3 complex via non-degradative ubiquitination.Cell discovery · 2023Article
- The Amyloid Precursor Protein Modulates the Position and Length of the Axon Initial Segment.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Implication of the cooking oil-peroxidation product "hydroxynonenal" for Alzheimer's disease.Frontiers in aging neuroscience · 2023Review
- Calpain signaling: from biology to therapeutic opportunities in neurodegenerative disorders.Frontiers in veterinary science · 2023Review
- Review
- Inhibition of Calpain Attenuates Degeneration of Substantia Nigra Neurons in the Rotenone Rat Model of Parkinson's Disease.International journal of molecular sciences · 2022Article
130 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Calcium-activated neutral proteinases (CANPs or calpains) are believed to be key enzymes in intracellular signaling cascades and potential mediators of calcium-induced neuronal degeneration. To investigate their involvement in Alzheimer disease, we identified three isoforms of muCANP (calpain I) in human postmortem brain corresponding to an 80-kDa precursor and two autolytically activated isoforms (78 and 76 kDa). As an index of changes in the in vivo activity of muCANP in Alzheimer disease, the ratio of the 76-kDa activated isoform of muCANP to its 80-kDa precursor was measured by immunoassay in selected brain regions from 22 individuals with Alzheimer disease and 18 normal controls. This muCANP activation ratio was elevated 3-fold in the prefrontal cortex from patients with Alzheimer disease but not from patients with Huntington disease. The activation ratio was also significantly elevated, but to a lesser degree, in brain regions where Alzheimer pathology is milder and has not led to overt neuronal degeneration. These findings indicate that muCANP activation is not simply a consequence of cellular degeneration but may be associated with dysfunction in many neurons before gross structural changes occur. The known influences of CANPs on cytoskeleton and membrane dynamics imply that persistent CANP activation may contribute to neurofibrillary pathology and abnormal amyloid precursor protein processing prior to causing synapse loss or cell death in the most vulnerable neuronal populations. Pharmacological modulation of the CANP system may merit consideration as a potential therapeutic strategy in Alzheimer disease.
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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.