ArticleProceedings of the National Academy of Sciences of the United States of America2021
Antipsychotic drugs counteract autophagy and mitophagy in multiple sclerosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- The dual role of mTOR in multiple sclerosis pathophysiology: a systematic review.Journal of neurology · 2026Pooled it
- Mitochondria-associated endoplasmic reticulum membranes and calcium ion exchange: A novel direction for aging and neurodegenerative diseases.Neural regeneration research · 2026Article
- Canonical and noncanonical autophagy in immunity.Immunity · 2026Review
- Mitochondrial quality control in health and disease: mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Mechanism of action and clinical application of autophagy in multiple sclerosis (Review).International journal of molecular medicine · 2026Review
- The importance of mitochondria and mitochondrial calcium signaling in health and disease: an updated outlook on inflammation.Journal of translational medicine · 2026Review
- A fixed mutation in the respiratory complex I impairs mitochondrial bioenergetics in the endangered Apennine brown bear.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Microglial Autophagy and Mitophagy in Ischemic Stroke: From Dual Roles to Therapeutic Modulation.Biology · 2025Review
- The Role of Autophagy in Long-term Effects of Spinal Cord Injury: Does Exosome Change the Autophagy Process and Vice Versa?Advanced pharmaceutical bulletin · 2025Review
- Mitochondrial Aging in the CNS: Unravelling Implications for Neurological Health and Disease.Biomolecules · 2025Review
- Pathogenetic Involvement of Autophagy and Mitophagy in Primary Progressive Multiple Sclerosis.Journal of cellular and molecular medicine · 2025Article
- System-level hypothesis of dopamine imbalance in early multiple sclerosis.Frontiers in neurology · 2025Article
- The role of autophagy in the pathogenesis and treatment of multiple sclerosis.Autophagy reports · 2025Review
- An Emerging Prospective of Antipsychotics for Treating Neurodegenerative Disorders.Current pharmaceutical design · 2025Review
- Receptor-mediated mitophagy: a new target of neurodegenerative diseases.Frontiers in neurology · 2025Review
- Emerging Insights into the Role of Macrophages in Multiple Sclerosis: Pathogenesis and Potential Therapeutic Strategies.Journal of inflammation research · 2025Review
- Article
- The Wolfram-like variant WFS1Autophagy · 2024Article
- Interactions Between Extracellular Vesicles and Autophagy in Neuroimmune Disorders.Neuroscience bulletin · 2024Review
- Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple sclerosis (MS) is a neuroinflammatory and neurodegenerative disease characterized by myelin damage followed by axonal and ultimately neuronal loss. The etiology and physiopathology of MS are still elusive, and no fully effective therapy is yet available. We investigated the role in MS of autophagy (physiologically, a controlled intracellular pathway regulating the degradation of cellular components) and of mitophagy (a specific form of autophagy that removes dysfunctional mitochondria). We found that the levels of autophagy and mitophagy markers are significantly increased in the biofluids of MS patients during the active phase of the disease, indicating activation of these processes. In keeping with this idea, in vitro and in vivo MS models (induced by proinflammatory cytokines, lysolecithin, and cuprizone) are associated with strongly impaired mitochondrial activity, inducing a lactic acid metabolism and prompting an increase in the autophagic flux and in mitophagy. Multiple structurally and mechanistically unrelated inhibitors of autophagy improved myelin production and normalized axonal myelination, and two such inhibitors, the widely used antipsychotic drugs haloperidol and clozapine, also significantly improved cuprizone-induced motor impairment. These data suggest that autophagy has a causal role in MS; its inhibition strongly attenuates behavioral signs in an experimental model of the disease. Therefore, haloperidol and clozapine may represent additional therapeutic tools against MS.
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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.