title: Human immunodeficiency virus-associated dementia: a link between accumulation of viral proteins and neuronal degeneration.
abstract: In the late stage of human immunodeficiency virus-1 (HIV) infection, a subset of individuals develops HIV associated neurocognitive disorders (HAND), which in its severe form, is characterized by motor and cognitive dysfunction. Dendritic pruning, synaptic abnormalities and neuronal apoptosis are observed in these patients. There are numerous advances in our understanding of HIV interactions with cells of the central nervous system. However, the underlying causes of neurological symptoms and pathological alterations observed in HIV positive subjects are poorly understood. Moreover, little is still known about the molecular mechanisms by which HIV induces synaptic dysfunction and degeneration. HAND resembles other common neurological diseases such as Alzheimer's and Huntington's diseases. These neurodegenerative disorders are characterized by accumulation of toxic proteins such as tau and huntingtin, respectively, which promote axonal degeneration by impairing axonal transport. Axonal degeneration precedes neuronal death. Therefore, a better understanding of the mechanisms whereby HIV triggers axonal degeneration has potential implications for developing therapeutic compounds to prevent synaptic failure in HAND. This article highlights and reviews evidence showing that neuronal accumulation of viral proteins promotes axonal damage.
authors.affiliation: Laboratory of Preclinical Neurobiology, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Italo
authors.initials: I
authors.lastname: Mocchetti
authors.affiliation: Laboratory of Preclinical Neurobiology, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Alessia
authors.initials: A
authors.lastname: Bachis
authors.affiliation: Department of Radiology, MedStar Georgetown University Hospital, Washington, DC, USA.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Esposito
authors.affiliation: Department of Neurology, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Scott R
authors.initials: SR
authors.lastname: Turner
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, USA.
authors.forename: Francesca
authors.initials: F
authors.lastname: Taraballi
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, USA.
authors.forename: Ennio
authors.initials: E
authors.lastname: Tasciotti
authors.affiliation: Department of Chemistry and Biochemistry, George Mason University, Fairfax, VA, USA.
authors.forename: Mikell
authors.initials: M
authors.lastname: Paige
authors.affiliation: Laboratory of Preclinical Neurobiology, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Valeriya
authors.initials: V
authors.lastname: Avdoshina
keywords: Alzheimer’s disease; HAND; HIV; axonal degeneration; brain-derived neurotrophic factor; gp120; microtubules; neurocognitive impairments