Neuropharmacologic Approaches to Restore the Brain’s Microenvironment

Li, Weizhe; Tong, Hsin I.; Gorantla, Santhi; Poluektova, Larisa Y.; Gendelman, Howard Eliot; Lu, Yuanan

doi:10.1007/s11481-016-9686-5

Cited by 10 publications

(5 citation statements)

References 97 publications

(113 reference statements)

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“…That role rests in utilizing the cell's own "high cytoplasmic content" to carry disease fighting drugs encased into stable nanoparticles (Edagwa et al, 2017). A discussion of the multifaceted MP in all its roles in health and disease has become the subject of this review with an eye towards how natural functions may be harnessed or even enhanced for the benefit of the host (Li et al, 2016). How the immune system affects its environment and vice versa characterize its multifaceted roles.…”

Section: Introductionmentioning

confidence: 99%

HIV and the Macrophage: From Cell Reservoirs to Drug Delivery to Viral Eradication

Herskovitz

Gendelman

2018

J Neuroimmune Pharmacol

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Macrophages serve as host cells, inflammatory disease drivers and drug runners for human immunodeficiency virus infection and treatments. Low-level viral persistence continues in these cells in the absence of macrophage death. However, the cellular microenvironment changes as a consequence of viral infection with aberrant production of pro-inflammatory factors and promotion of oxidative stress. These herald viral spread from macrophages to neighboring CD4 T cells and end organ damage. Virus replicates in tissue reservoir sites that include the nervous, pulmonary, cardiovascular, gut, and renal organs. However, each of these events are held in check by antiretroviral therapy. A hidden and often overlooked resource of the macrophage rests in its high cytoplasmic nuclear ratios that allow the cell to sense its environment and rid it of the cellular waste products and microbial pathogens it encounters. These phagocytic and intracellular killing sensing mechanisms can also be used in service as macrophages serve as cellular carriage depots for antiretroviral nanoparticles and are able to deliver medicines to infectious disease sites with improved therapeutic outcomes. These undiscovered cellular functions can lead to reductions in persistent infection and may potentially facilitate the eradication of residual virus to eliminate disease.

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Section: Introductionmentioning

confidence: 99%

HIV and the Macrophage: From Cell Reservoirs to Drug Delivery to Viral Eradication

Herskovitz

Gendelman

2018

J Neuroimmune Pharmacol

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“…In the CNS, microglia acted as the first and main immune defense against infectious and pathological events [ 8 ]. They could promptly survey changes of the surroundings and sense extracellular messengers via cell surface receptors [ 9 ], subsequently congregate together rapidly to build a protective barrier between normal and damaged tissues [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Nucleotide transmitters ATP and ADP mediate intercellular calcium wave communication via P2Y12/13 receptors among BV-2 microglia

et al. 2017

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Nerve injury is accompanied by a liberation of diverse nucleotides, some of which act as ‘find/eat-me’ signals in mediating neuron-glial interplay. Intercellular Ca2+ wave (ICW) communication is the main approach by which glial cells interact and coordinate with each other to execute immune defense. However, the detailed mechanisms on how these nucleotides participate in ICW communication remain largely unclear. In the present work, we employed a mechanical stimulus to an individual BV-2 microglia to simulate localized injury. Remarkable ICW propagation was observed no matter whether calcium was in the environment or not. Apyrase (ATP/ADP-hydrolyzing enzyme), suramin (broad-spectrum P2 receptor antagonist), 2-APB (IP3 receptor blocker) and thapsigargin (endoplasmic reticulum calcium pump inhibitor) potently inhibited these ICWs, respectively, indicating the dependence of nucleotide signals and P2Y receptors. Then, we detected the involvement of five naturally occurring nucleotides (ATP, ADP, UTP, UDP and UDP-glucose) by desensitizing receptors. Results showed that desensitization with ATP and ADP could block ICW propagation in a dose-dependent manner, whereas other nucleotides had little effect. Meanwhile, the expression of P2Y receptors in BV-2 microglia was identified and their contributions were analyzed, from which we suggested P2Y12/13 receptors activation mostly contributed to ICWs. Besides, we estimated that extracellular ATP and ADP concentration sensed by BV-2 microglia was about 0.3 μM during ICWs by analyzing calcium dynamic characteristics. Taken together, these results demonstrated that the nucleotides ATP and ADP were predominant signal transmitters in mechanical stimulation-induced ICW communication through acting on P2Y12/13 receptors in BV-2 microglia.

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“…AGEs can interact with the receptor for AGE to promote ROS production or via NF-κB signaling pathways to express proinflammatory cytokines, such as TNF-α and IL-6 (Calcutt et al 2009). The continuous inflammations in neuron cells can induce cell damages and gradually develop the neurodegenerative disorders, such as Alzheimer’s disease and Parkinson’s disease (Li et al 2016). The iNOS protein expressions (Fig.…”

Section: Discussionmentioning

confidence: 99%

Anti-glycation, anti-hemolysis, and ORAC activities of demethylcurcumin and tetrahydroxycurcumin in vitro and reductions of oxidative stress in d-galactose-induced BALB/c mice in vivo

et al. 2019

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Background There were few report concerning anti-glycation and antioxidant activities of the minor amounts of components in curcuminoids, demethylcurcumin and tetrahydroxycurcumin, in vitro and in vivo. Results The bovine serum albumin/galactose of non-enzymatic glycation models, radical-induced hemolysis, and oxygen radical absorbance capacity (ORAC) were studied in vitro, and the d-galactose-induced oxidative stress in BALB/c mice and then demethylcurcumin or tetrahydroxycurcumin interventions in vivo. The parameters of oxidative stress in plasma and brain extracts were determined among animal groups with or without both curcuminoids interventions. The demethylcurcumin and tetrahydroxycurcumin exhibited anti-glycation, anti-hemolysis, and ORAC activities, and showed much better and significant difference (P < 0.05) compared to those of curcumin in vitro. In animal experiments, the intervened two curcuminoids at both concentrations showed to lower serum malondialdehyde (MDA), brain MDA levels and iNOS protein expressions, and elevate serum ORAC activities, and showed difference (P < 0.05) compared to the galactose-induced control. Conclusion The demethylcurcumin and tetrahydroxycurcumin showed potentials in developing functional foods for antioxidant-related purposes.

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Neuropharmacologic Approaches to Restore the Brain’s Microenvironment

Cited by 10 publications

References 97 publications

HIV and the Macrophage: From Cell Reservoirs to Drug Delivery to Viral Eradication

HIV and the Macrophage: From Cell Reservoirs to Drug Delivery to Viral Eradication

Nucleotide transmitters ATP and ADP mediate intercellular calcium wave communication via P2Y12/13 receptors among BV-2 microglia

Anti-glycation, anti-hemolysis, and ORAC activities of demethylcurcumin and tetrahydroxycurcumin in vitro and reductions of oxidative stress in d-galactose-induced BALB/c mice in vivo

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