The far-reaching HAND of cART : cART effects on astrocytes
Following the introduction of combination antiretroviral therapy (cART), the morbidity and mortality from human immunodeficiency virus (HIV) infection has been drastically curtailed and HIV has now become a chronic manageable disease. Persons living with HIV (PLWH) are living longer and experiencing significant co-morbidities and conditions of aging. NeuroHIV, clinically defined as HIV-Associated Neurocognitive Disorders (HAND) and pathologically manifested by persistent inflammation in the CNS despite cART, is a significant co-morbid condition for PLWH. In the pre-cART era, HIV mediated much of the pathogenesis in the Central Nervous System (CNS); in the cART era, with low to undetectable viremia, other mechanisms may be contributing to persistent neuroinflammation. Emerging data point to the adverse effects at the cellular level of cART, independent of HIV. Astrocytes are the most abundant cells in the CNS, playing vital roles in maintaining CNS homeostasis (e.g. metabolic support to neurons, clearance of neurotransmitters, ion balance, modulation of synaptic functions and maintaining the structural integrity of the blood brain barrier (BBB). Therefore, any disruption of their function will have wide repercussions in the CNS. In this review, we will address current knowledge and gaps on the impact of antiretrovirals (ARVs) on astrocytes and physiologic consequences in the CNS. Understanding the status of this field, will provide a practical framework to elucidate the potential role of cART-mediated dysregulation of astrocytes in neuroHIV pathogenesis and inform therapeutic strategies that are "neuro-friendly". Graphical abstract CNS-penetrating cART have the potential to cause resting astrocytes to become activated into an A1 or neurotoxic phenotype. These cells can in turn secrete inflammatory cytokines that affect surrounding microglia macrophages, as well as neurotoxic factors that impact nearby neurons. In addition, impairment in the physiologic functions of astrocytes will result in altered BBB permeability and disrupted metabolic homeostasis. CNS=Central Nervous System; cART=combined antiretroviral therapy; BBB=blood brain barrier.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:16 |
|---|---|
| Enthalten in: |
Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology - 16(2021), 1 vom: 09. März, Seite 144-158 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Gonzalez, Hemil [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
0RH81L854J |
|---|
| Anmerkungen: |
Date Completed 22.11.2021 Date Revised 16.07.2022 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1007/s11481-020-09907-w |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM307361616 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM307361616 | ||
| 003 | DE-627 | ||
| 005 | 20231225125409.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1007/s11481-020-09907-w |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1024.xml |
| 035 | |a (DE-627)NLM307361616 | ||
| 035 | |a (NLM)32147775 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Gonzalez, Hemil |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The far-reaching HAND of cART |b cART effects on astrocytes |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 22.11.2021 | ||
| 500 | |a Date Revised 16.07.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Following the introduction of combination antiretroviral therapy (cART), the morbidity and mortality from human immunodeficiency virus (HIV) infection has been drastically curtailed and HIV has now become a chronic manageable disease. Persons living with HIV (PLWH) are living longer and experiencing significant co-morbidities and conditions of aging. NeuroHIV, clinically defined as HIV-Associated Neurocognitive Disorders (HAND) and pathologically manifested by persistent inflammation in the CNS despite cART, is a significant co-morbid condition for PLWH. In the pre-cART era, HIV mediated much of the pathogenesis in the Central Nervous System (CNS); in the cART era, with low to undetectable viremia, other mechanisms may be contributing to persistent neuroinflammation. Emerging data point to the adverse effects at the cellular level of cART, independent of HIV. Astrocytes are the most abundant cells in the CNS, playing vital roles in maintaining CNS homeostasis (e.g. metabolic support to neurons, clearance of neurotransmitters, ion balance, modulation of synaptic functions and maintaining the structural integrity of the blood brain barrier (BBB). Therefore, any disruption of their function will have wide repercussions in the CNS. In this review, we will address current knowledge and gaps on the impact of antiretrovirals (ARVs) on astrocytes and physiologic consequences in the CNS. Understanding the status of this field, will provide a practical framework to elucidate the potential role of cART-mediated dysregulation of astrocytes in neuroHIV pathogenesis and inform therapeutic strategies that are "neuro-friendly". Graphical abstract CNS-penetrating cART have the potential to cause resting astrocytes to become activated into an A1 or neurotoxic phenotype. These cells can in turn secrete inflammatory cytokines that affect surrounding microglia macrophages, as well as neurotoxic factors that impact nearby neurons. In addition, impairment in the physiologic functions of astrocytes will result in altered BBB permeability and disrupted metabolic homeostasis. CNS=Central Nervous System; cART=combined antiretroviral therapy; BBB=blood brain barrier | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Review | |
| 650 | 4 | |a ARVs | |
| 650 | 4 | |a Astrocytes | |
| 650 | 4 | |a HAND | |
| 650 | 4 | |a Neurotoxicity | |
| 650 | 4 | |a cART | |
| 650 | 7 | |a Anti-HIV Agents |2 NLM | |
| 650 | 7 | |a Glutamine |2 NLM | |
| 650 | 7 | |a 0RH81L854J |2 NLM | |
| 650 | 7 | |a Glutamic Acid |2 NLM | |
| 650 | 7 | |a 3KX376GY7L |2 NLM | |
| 650 | 7 | |a Glucose |2 NLM | |
| 650 | 7 | |a IY9XDZ35W2 |2 NLM | |
| 650 | 7 | |a Calcium |2 NLM | |
| 650 | 7 | |a SY7Q814VUP |2 NLM | |
| 700 | 1 | |a Podany, Anthony |e verfasserin |4 aut | |
| 700 | 1 | |a Al-Harthi, Lena |e verfasserin |4 aut | |
| 700 | 1 | |a Wallace, Jennillee |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology |d 2006 |g 16(2021), 1 vom: 09. März, Seite 144-158 |w (DE-627)NLM175377324 |x 1557-1904 |7 nnns |
| 773 | 1 | 8 | |g volume:16 |g year:2021 |g number:1 |g day:09 |g month:03 |g pages:144-158 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1007/s11481-020-09907-w |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 16 |j 2021 |e 1 |b 09 |c 03 |h 144-158 | ||