Extracellular Vesicles: A Possible Link between HIV and Alzheimer’s Disease-Like Pathology in HIV Subjects?
The longevity of people with HIV/AIDS has been prolonged with the use of antiretroviral therapy (ART). The age-related complications, especially cognitive deficits, rise as HIV patients live longer. Deposition of beta-amyloid (Aβ), a hallmark of Alzheimer’s disease (AD), has been observed in subject...
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| Format: | Article |
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MDPI AG
2019-08-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/8/9/968 |
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| author | Sunitha Kodidela Kelli Gerth Sanjana Haque Yuqing Gong Saifudeen Ismael Ajay Singh Ishrat Tauheed Santosh Kumar |
| author_facet | Sunitha Kodidela Kelli Gerth Sanjana Haque Yuqing Gong Saifudeen Ismael Ajay Singh Ishrat Tauheed Santosh Kumar |
| author_sort | Sunitha Kodidela |
| collection | DOAJ |
| description | The longevity of people with HIV/AIDS has been prolonged with the use of antiretroviral therapy (ART). The age-related complications, especially cognitive deficits, rise as HIV patients live longer. Deposition of beta-amyloid (Aβ), a hallmark of Alzheimer’s disease (AD), has been observed in subjects with HIV-associated neurocognitive disorders (HAND). Various mechanisms such as neuroinflammation induced by HIV proteins (e.g., Tat, gp120, Nef), excitotoxicity, oxidative stress, and the use of ART contribute to the deposition of Aβ, leading to dementia. However, progressive dementia in older subjects with HIV might be due to HAND, AD, or both. Recently, extracellular vesicles (EVs)/exosomes, have gained recognition for their importance in understanding the pathology of both HAND and AD. EVs can serve as a possible link between HIV and AD, due to their ability to package and transport the toxic proteins implicated in both AD and HIV (Aβ/tau and gp120/tat, respectively). Given that Aß is also elevated in neuron-derived exosomes isolated from the plasma of HIV patients, it is reasonable to suggest that neuron-to-neuron exosomal transport of Aβ and tau also contributes to AD-like pathology in HIV-infected subjects. Therefore, exploring exosomal contents is likely to help distinguish HAND from AD. However, future prospective clinical studies need to be conducted to compare the exosomal contents in the plasma of HIV subjects with and without HAND as well as those with and without AD. This would help to find new markers and develop new treatment strategies to treat AD in HIV-positive subjects. This review presents comprehensive literatures on the mechanisms contributing to Aβ deposition in HIV-infected cells, the role of EVs in the propagation of Aβ in AD, the possible role of EVs in HIV-induced AD-like pathology, and finally, possible therapeutic targets or molecules to treat HIV subjects with AD. |
| first_indexed | 2024-03-12T10:41:00Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T10:41:00Z |
| publishDate | 2019-08-01 |
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| record_format | Article |
| series | Cells |
| spelling | doaj.art-ba34a1f259314f39a77314517fbe46012023-09-02T08:10:52ZengMDPI AGCells2073-44092019-08-018996810.3390/cells8090968cells8090968Extracellular Vesicles: A Possible Link between HIV and Alzheimer’s Disease-Like Pathology in HIV Subjects?Sunitha Kodidela0Kelli Gerth1Sanjana Haque2Yuqing Gong3Saifudeen Ismael4Ajay Singh5Ishrat Tauheed6Santosh Kumar7Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Ave, Memphis, TN 38163, USADepartment of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Ave, Memphis, TN 38163, USADepartment of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Ave, Memphis, TN 38163, USADepartment of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Ave, Memphis, TN 38163, USADepartment of Anatomy and Neurobiology, The University of Tennessee Health Science Center, 855 Monroe Avenue #515, Memphis, TN 38163, USADepartment of Pediatric Pulmonology, Le Bonheur Children Hospital, 50 N. Dunlap st, Memphis, TN 38103, USADepartment of Anatomy and Neurobiology, The University of Tennessee Health Science Center, 855 Monroe Avenue #515, Memphis, TN 38163, USADepartment of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Ave, Memphis, TN 38163, USAThe longevity of people with HIV/AIDS has been prolonged with the use of antiretroviral therapy (ART). The age-related complications, especially cognitive deficits, rise as HIV patients live longer. Deposition of beta-amyloid (Aβ), a hallmark of Alzheimer’s disease (AD), has been observed in subjects with HIV-associated neurocognitive disorders (HAND). Various mechanisms such as neuroinflammation induced by HIV proteins (e.g., Tat, gp120, Nef), excitotoxicity, oxidative stress, and the use of ART contribute to the deposition of Aβ, leading to dementia. However, progressive dementia in older subjects with HIV might be due to HAND, AD, or both. Recently, extracellular vesicles (EVs)/exosomes, have gained recognition for their importance in understanding the pathology of both HAND and AD. EVs can serve as a possible link between HIV and AD, due to their ability to package and transport the toxic proteins implicated in both AD and HIV (Aβ/tau and gp120/tat, respectively). Given that Aß is also elevated in neuron-derived exosomes isolated from the plasma of HIV patients, it is reasonable to suggest that neuron-to-neuron exosomal transport of Aβ and tau also contributes to AD-like pathology in HIV-infected subjects. Therefore, exploring exosomal contents is likely to help distinguish HAND from AD. However, future prospective clinical studies need to be conducted to compare the exosomal contents in the plasma of HIV subjects with and without HAND as well as those with and without AD. This would help to find new markers and develop new treatment strategies to treat AD in HIV-positive subjects. This review presents comprehensive literatures on the mechanisms contributing to Aβ deposition in HIV-infected cells, the role of EVs in the propagation of Aβ in AD, the possible role of EVs in HIV-induced AD-like pathology, and finally, possible therapeutic targets or molecules to treat HIV subjects with AD.https://www.mdpi.com/2073-4409/8/9/968HIVexosomesextracellular vesicles (EVs)beta-amyloidAlzheimer’s diseaseneurodegenerationHANDHIV-TAT |
| spellingShingle | Sunitha Kodidela Kelli Gerth Sanjana Haque Yuqing Gong Saifudeen Ismael Ajay Singh Ishrat Tauheed Santosh Kumar Extracellular Vesicles: A Possible Link between HIV and Alzheimer’s Disease-Like Pathology in HIV Subjects? Cells HIV exosomes extracellular vesicles (EVs) beta-amyloid Alzheimer’s disease neurodegeneration HAND HIV-TAT |
| title | Extracellular Vesicles: A Possible Link between HIV and Alzheimer’s Disease-Like Pathology in HIV Subjects? |
| title_full | Extracellular Vesicles: A Possible Link between HIV and Alzheimer’s Disease-Like Pathology in HIV Subjects? |
| title_fullStr | Extracellular Vesicles: A Possible Link between HIV and Alzheimer’s Disease-Like Pathology in HIV Subjects? |
| title_full_unstemmed | Extracellular Vesicles: A Possible Link between HIV and Alzheimer’s Disease-Like Pathology in HIV Subjects? |
| title_short | Extracellular Vesicles: A Possible Link between HIV and Alzheimer’s Disease-Like Pathology in HIV Subjects? |
| title_sort | extracellular vesicles a possible link between hiv and alzheimer s disease like pathology in hiv subjects |
| topic | HIV exosomes extracellular vesicles (EVs) beta-amyloid Alzheimer’s disease neurodegeneration HAND HIV-TAT |
| url | https://www.mdpi.com/2073-4409/8/9/968 |
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