The DOI matches its Crossref record; 80 of the 80 references it cites were found in a registry or an index.
Protein Kinase C Inhibitors: Rationale for Use and Potential in the Treatment of Bipolar Disorder
Open accessAbstract
Bipolar disorder is one of the most severely debilitating of all medical illnesses. For a large number of patients, outcomes are quite poor. The illness results in tremendous suffering for patients and their families and commonly impairs functioning and workplace productivity. Risks of increased morbidity and mortality, unfortunately, are frequent occurrences as well. Until recently, little has been known about the specific molecular and cellular underpinnings of bipolar disorder. Such knowledge is crucial for the prospect of developing specific targeted therapies that are more effective and that have a more rapid onset of action than currently available treatments. Exciting recent data suggest that regulation of certain signalling pathways may be involved in the aetiology of bipolar disorder and that these pathways may be profitably targeted to treat the disorder. In particular, mania is associated with overactive protein kinase C (PKC) intracellular signalling, and recent genome-wide association studies of bipolar disorder have implicated an enzyme that reduces the activation of PKC. Importantly, the current mainstays in the treatment of mania, lithium (a monovalent cation) and valproate (a small fatty acid) indirectly inhibit PKC. In addition, recent clinical studies with the relatively selective PKC inhibitor tamoxifen add support to the relevance of the PKC target in bipolar disorder. Overall, a growing body of work both on a preclinical and clinical level indicates that PKC signalling may play an important role in the pathophysiology and treatment of bipolar disorder. The development of CNS-penetrant PKC inhibitors may have considerable benefit for this devastating illness.
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“PKC inhibitor tamoxifen enhances the capacity of lithium to reduce symptoms of mania in BD [105–107].”
From Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation (2019) · cites this paper as [105]
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“Treatment of BD patients with lithium or valproate inhibits PKC upregulation, normalizing its level to that of euthymic subjects, and increases BDNF levels [105].”
From Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation (2019) · cites this paper as [105]
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Cites
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Factors allowing small monovalent Li + to displace Ca 2+ in proteins
Grauffel, C., Weng, W.-H., & Lim, C. (2022) · Physical Chemistry Chemical Physics · doi:10.1039/d2cp02072f · Cited by 1
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Metadata
- Authors
- Zarate, C. A., & Manji, H. K.
- Affiliations
- National Institutes of Health (US)
- National Institute of Mental Health (US)
- Corresponding author
- Zarate, Carlos A.
- Venue
- CNS Drugs
- Published
- 2009-07
- Volume
- 23
- Issue
- 7
- Pages
- 569-582
- ISSN
- 1172-7047 (ISSN-L)
- PMC
- PMC2802274
- OpenAlex
- W2139699538
- Cited by
- 122
- References
- 80
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 3 · 2022: 7 · 2021: 8 · 2020: 7 · 2019: 10 · 2018: 5 · 2017: 13 · 2016: 6 · 2015: 6 · 2014: 10 · 2013: 7 · 2012: 12
- FWCI
- 1.30
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- CNS Drugs (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (Z01MH002830)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- protein kinase C, PKC inhibitors, bipolar disorder, mania, lithium, valproic acid, tamoxifen, targeted therapy, genome-wide association study
- MeSH terms
- Animals, Bipolar Disorder, Clinical Trials as Topic, Humans, Models, Biological, Protein Kinase C, Antimanic Agents, Protein Kinase Inhibitors
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