Extracellular Vesicles: A Possible Link between HIV and Alzheimer’s Disease-Like Pathology in HIV Subjects?

Kumar, Santosh; Gerth, Kelli; Haque, Sanjana; Gong, Yuqing; Ismael, Saifudeen; Singh, Ajay K.; Ishrat, Tauheed; Kumar, Santosh

doi:10.3390/cells8090968

Cited by 41 publications

(48 citation statements)

References 150 publications

(199 reference statements)

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“…Moreover, radio-and chemotherapy may also influence the development of treatment-resistant cancer cells [75], possibly through cellular reprogramming [109] and/or the formation of brain metastasis [110]. Genetics [54,111], age [71], existing comorbidities [112,113], lifestyle [114,115], and environmental [116] factors are likely to alter the extracellular fate of exosomes, which leads to CRCI (Figure 2). Changes in exosomal cargo content and their release may further influence diverse mechanisms/pathways capable of impacting the brain and CNS function, which could result in CRCI (Figure 3).…”

Section: Mechanisms Associated With Exosomes and Crcimentioning

confidence: 99%

“…Although the precise mechanisms underlying CRCI remain to be established, several studies suggest there is a link between exosomes and CRCI. Exosome biogenesis, its cargo content, function, and activity may be influenced by cancer [97], cancer therapies [93,102], genetics [54,111], age [71], existing comorbidities [112,113], lifestyle [114,115], and environmental [116] factors. Differences in exosomal content (e.g., miRNAs and proteins) and release may exert protective or damaging effects that could alter the brain and CNS function, and cause declining cognitive health in cancer survivors.…”

Section: Potential Implication Of Exosomes In Crci Researchmentioning

confidence: 99%

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Role of Exosomes in Cancer-Related Cognitive Impairment

Koh

Tan

Toh

et al. 2020

IJMS

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A decline in cognitive function following cancer treatment is one of the most commonly reported post-treatment symptoms among patients with cancer and those in remission, and include memory, processing speed, and executive function. A clear understanding of cognitive impairment as a result of cancer and its therapy can be obtained by delineating structural and functional changes using brain imaging studies and neurocognitive assessments. There is also a need to determine the underlying mechanisms and pathways that impact the brain and affect cognitive functioning in cancer survivors. Exosomes are small cell-derived vesicles formed by the inward budding of multivesicular bodies, and are released into the extracellular environment via an exocytic pathway. Growing evidence suggests that exosomes contribute to various physiological and pathological conditions, including neurological processes such as synaptic plasticity, neuronal stress response, cell-to-cell communication, and neurogenesis. In this review, we summarize the relationship between exosomes and cancer-related cognitive impairment. Unraveling exosomes' actions and effects on the microenvironment of the brain, which impacts cognitive functioning, is critical for the development of exosome-based therapeutics for cancer-related cognitive impairment.Int. J. Mol. Sci. 2020, 21, 2755 2 of 16 attention, learning, and executive function [10]. CRCI adversely affects cancer patients and survivors, causing distress and reduced quality of life, and impacts many facets of their daily lives [11]. CRCI is complicated by many factors including the direct effects of cancer, genetic predisposition (e.g., carrier of apolipoprotein E type epsilon 4 allele [12] and brain-derived neurotrophic factor Met allele [13]), comorbidities independent of the actual disease, and/or treatments or combinations of treatments administered for the disease [14].Efforts to better understand cancer-and cancer-therapy-associated cognitive impairment have relied on methods ranging from cognitive functioning assessment to imaging technologies on brain structure and function (e.g., magnetic resonance imaging scan). However, these approaches may be limited to help us understand the etiology and pathophysiology of cognitive dysfunction. The emerging application of the use of liquid biopsies (e.g., plasma and cerebrospinal fluid) as a strategy for biomarker discovery to detect, assess and monitor CRCI is fast-expanding and evolving [15,16]. In published literature, studies have revealed that genetics and neurobiological and immunological mechanisms may be involved in the biogenesis and development of CRCI. Preclinical studies have also provided insights into the pathophysiological mechanisms underlying CRCI, including neurotoxicity and inflammatory factors, which were shown to be responsible for CRCI [17]. Nevertheless, the underlying mechanisms of CRCI have yet to be established. While the role of exosomes in cancer has been well-documented [18][19][20], the role of cancer exosomes and their ability ...

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Section: Mechanisms Associated With Exosomes and Crcimentioning

confidence: 99%

Section: Potential Implication Of Exosomes In Crci Researchmentioning

confidence: 99%

Role of Exosomes in Cancer-Related Cognitive Impairment

Koh

Tan

Toh

et al. 2020

IJMS

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“…Moreover, PLWHA have a significantly higher rate of neurocognitive disorders. As mentioned, Aβ deposition is an indicator of Alzheimer's disease, which was also identified in the EVs of HIV positive individuals, suggesting the possibility of using Aβ in EVs as a biomarker [119].…”

Section: Evs In Hivmentioning

confidence: 83%

“…HIV-associated neurocognitive disorder, demonstrated by Aβ deposition, is highly common in PLWHA, which is a well-established biomarker for Alzheimer's disease. Interestingly, neuron derived EVs from HIV populations show high levels of Aβ, which can serve as a possible biomarker for Alzheimer's disease in PLWHA [119,120]. Markers of general neurodegeneration, e.g.…”

Section: Advances Since 2015mentioning

confidence: 99%

Extracellular Vesicles in Smoking-Mediated HIV Pathogenesis and their Potential Role in Biomarker Discovery and Therapeutic Interventions

Haque

Kumar

Gerth

et al. 2020

Cells

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In the last two decades, the mortality rate in people living with HIV/AIDS (PLWHA) has decreased significantly, resulting in an almost normal longevity in this population. However, a large portion of this population still endures a poor quality of life, mostly due to an increased inclination for substance abuse, including tobacco smoking. The prevalence of smoking in PLWHA is consistently higher than in HIV negative persons. A predisposition to cigarette smoking in the setting of HIV potentially leads to exacerbated HIV replication and a higher risk for developing neurocognitive and other CNS disorders. Oxidative stress and inflammation have been identified as mechanistic pathways in smoking-mediated HIV pathogenesis and HIV-associated neuropathogenesis. Extracellular vesicles (EVs), packaged with oxidative stress and inflammatory agents, show promise in understanding the underlying mechanisms of smoking-induced HIV pathogenesis via cell-cell interactions. This review focuses on recent advances in the field of EVs with an emphasis on smoking-mediated HIV pathogenesis and HIV-associated neuropathogenesis. This review also provides an overview of the potential applications of EVs in developing novel therapeutic carriers for the treatment of HIV-infected individuals who smoke, and in the discovery of novel biomarkers that are associated with HIV-smoking interactions in the CNS.

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“…Exosomes could, therefore, help in regulating damaged processes within our bodies. Patients with chronic inflammation, autoimmune diseases and other chronic degenerative diseases may benefit from including exosomes in their treatment [28][29][30]. Currently, exosome therapy is also used to treat orthopedic injuries and for anti-aging management [31,32], indicating that exosomes are reaching a wider use in regenerative medicine.…”

Section: Stem Cell-derived Exosomes As Tool For Cell-free Therapymentioning

confidence: 99%

Stem Cell-Derived Exosomes in Autism Spectrum Disorder

Alessio

Brigida²,

Peluso

et al. 2020

IJERPH

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Neurodevelopmental lifelong pathologies defined by problems with social interaction, communication capacity and presence of repetitive/stereotyped clusters of behavior and interests are grouped under the definition of autism spectrum disorder (ASD). ASD prevalence is still increasing, indicating the need to identify specific biomarkers and novel pharmacotherapies. Neuroinflammation and neuro-immune cross-talk dysregulation are specific hallmarks of ASD, offering the possibility of treating these disorders by stem cell therapy. Indeed, cellular strategies have been postulated, proposed and applied to ASD. However, less is known about the molecular action mechanisms of stem cells. As a possibility, the positive and restorative effects mediated by stem cells could be due to their paracrine activity, by which stem cells produce and release several ameliorative and anti-inflammatory molecules. Among the secreted complex tools, exosomes are sub-organelles, enriched by RNA and proteins, that provide cell-to-cell communication. Exosomes could be the mediators of many stem cell-associated therapeutic activities. This review article describes the potential role of exosomes in alleviating ASD symptoms.

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Extracellular Vesicles: A Possible Link between HIV and Alzheimer’s Disease-Like Pathology in HIV Subjects?

Cited by 41 publications

References 150 publications

Role of Exosomes in Cancer-Related Cognitive Impairment

Role of Exosomes in Cancer-Related Cognitive Impairment

Extracellular Vesicles in Smoking-Mediated HIV Pathogenesis and their Potential Role in Biomarker Discovery and Therapeutic Interventions

Stem Cell-Derived Exosomes in Autism Spectrum Disorder

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