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Journal article
Mechanisms of neuronal dysfunction in HIV-associated neurocognitive disorders
Cellular and molecular life sciences : CMLS, v 78(9), pp 4283-4303
2021
PMID: 33585975
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
HIV-associated neurocognitive disorder (HAND) is characterized by cognitive and behavioral deficits in people living with HIV. HAND is still common in patients that take antiretroviral therapies, although they tend to present with less severe symptoms. The continued prevalence of HAND in treated patients is a major therapeutic challenge, as even minor cognitive impairment decreases patient’s quality of life. Therefore, modern HAND research aims to broaden our understanding of the mechanisms that drive cognitive impairment in people with HIV and identify promising molecular pathways and targets that could be exploited therapeutically. Recent studies suggest that HAND in treated patients is at least partially induced by subtle synaptodendritic damage and disruption of neuronal networks in brain areas that mediate learning, memory, and executive functions. Although the causes of subtle neuronal dysfunction are varied, reversing synaptodendritic damage in animal models restores cognitive function and thus highlights a promising therapeutic approach. In this review, we examine evidence of synaptodendritic damage and disrupted neuronal connectivity in HAND from clinical neuroimaging and neuropathology studies and discuss studies in HAND models that define structural and functional impairment of neurotransmission. Then, we report molecular pathways, mechanisms, and comorbidities involved in this neuronal dysfunction, discuss new approaches to reverse neuronal damage, and highlight current gaps in knowledge. Continued research on the manifestation and mechanisms of synaptic injury and network dysfunction in HAND patients and experimental models will be critical if we are to develop safe and effective therapies that reverse subtle neuropathology and cognitive impairment.
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Details
- Title
- Mechanisms of neuronal dysfunction in HIV-associated neurocognitive disorders
- Creators
- Elena Irollo - Drexel UniversityJared Luchetta - Drexel UniversityChunta Ho - Drexel UniversityBradley Nash - Drexel UniversityOlimpia Meucci - Drexel University
- Publication Details
- Cellular and molecular life sciences : CMLS, v 78(9), pp 4283-4303
- Publisher
- Springer International Publishing
- Grant note
- DA015014; DA032444 / National Institute on Drug Abuse (http://dx.doi.org/10.13039/100000026) MH079785 (Training grant) / National Institute of Mental Health (http://dx.doi.org/10.13039/100000025)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000617841000002
- Scopus ID
- 2-s2.0-85100861438
- Other Identifier
- 991019168347404721
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- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology