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Published on: February 21, 2019
Neuroprotective versus tumorigenic protein kinase C activators
1Blanchette Rockefeller Neurosciences Institute, West Virginia University School of Medicine, Morgantown, WV 26506, USA. tjnelson@brneurosci.org
Protein kinase C (PKC) activators show promise for neurological disorders by promoting neuron repair and function. Non-tumorigenic activators at low doses may offer therapeutic benefits for conditions like Alzheimer's and stroke.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Protein kinase C (PKC) activators exhibit neurotrophic and neuroprotective effects, suggesting therapeutic potential for neurodegenerative diseases, stroke, and brain injury.
- While some PKC activators are explored as anti-cancer agents, others, like phorbol esters, act as tumor promoters.
- PKC activators can lead to downregulation of PKC, particularly PKCdelta, at high concentrations or prolonged exposure, with tumorigenic activators showing a stronger effect on specific isozymes.
Purpose of the Study:
- To explore the therapeutic potential of Protein Kinase C (PKC) activators in neurological disorders.
- To differentiate the effects of tumorigenic versus non-tumorigenic PKC activators.
- To identify optimal conditions for utilizing PKC activators to maximize therapeutic benefits while minimizing adverse effects.
Main Methods:
- Investigated the neurotrophic and neuroprotective activities of various Protein Kinase C (PKC) activators.
- Compared the effects of different PKC activators on PKC isozyme downregulation, focusing on PKCdelta.
- Analyzed structural features of tumorigenic PKC activators.
- Assessed the impact of PKC activators at concentrations minimizing downregulation on neuronal repair, memory, and cell proliferation.
Main Results:
- PKC activators demonstrate neurotrophic and neuroprotective properties beneficial for neurological conditions.
- Tumorigenic PKC activators exhibit distinct structural features and cause stronger downregulation of specific PKC isozymes, like PKCdelta.
- At low concentrations that minimize PKC downregulation, these activators can enhance memory, reduce beta-amyloid, promote synaptogenesis, and aid neuronal repair.
Conclusions:
- Structurally specific, non-tumorigenic Protein Kinase C (PKC) activators, when used intermittently at low concentrations, may offer significant therapeutic advantages for neurological disorders.
- These findings suggest a potential therapeutic window for PKC activators in treating conditions such as Alzheimer's disease, stroke, and traumatic brain injury.
- Further research into the specific mechanisms and structural requirements of non-tumorigenic PKC activators is warranted for clinical translation.
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