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Interactions between integrase inhibitors and human arginase 1.
Lucia Lisi1, Michela Pizzoferrato1, Fabiola Teresa Miscioscia2
1Institute of Pharmacology, Catholic University Medical School, Rome, Italy.
Journal of Neurochemistry
|April 12, 2017
Summary
Integrase strand transfer inhibitors like Dolutegravir, Raltegravir, and Elvitegravir can inhibit arginase activity. This finding may offer new insights into managing HIV-associated neurocognitive disorders by targeting microglia activation.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- The mechanisms behind HIV-associated neurocognitive disorders are largely unknown.
- HIV-infected macrophages and microglia are key players, with l-arginine metabolism potentially influencing microglia activation.
- Arginase (ARG) utilizes l-arginine and is implicated in oxidative stress and inflammation.
Purpose of the Study:
- To investigate if integrase strand transfer inhibitors (INSTIs) inhibit arginase (ARG) activity.
- To explore the potential of INSTIs as modulators of ARG activity in the context of HIV neuroinflammation.
Main Methods:
- Utilized a validated human microglia cell line model.
- Employed computational chemistry approaches.
- Characterized purified human ARG activity in a cell-free in vitro system.
- Assessed the effects of specific INSTIs on ARG activity.
Main Results:
- Dolutegravir, Raltegravir, and Elvitegravir demonstrated inhibition of arginase activity.
- The study validated a new cell-free in vitro system for studying ARG inhibitors.
Conclusions:
- Integrase strand transfer inhibitors show potential in inhibiting arginase activity.
- These findings contribute to understanding the neuroprotective effects of certain antiretroviral drugs.
- Targeting arginase may be a viable strategy in addressing HIV-associated neurocognitive disorders.