The role of human dopamine transporter in NeuroAIDS

Jun Zhu, Subramaniam Ananthan, Chang Guo Zhan

Research output: Contribution to journalReview articlepeer-review

19 Scopus citations


HIV-associated neurocognitive disorder (HAND) remains highly prevalent in HIV infected individuals and represents a special group of neuropathological disorders, which are associated with HIV-1 viral proteins, such as transactivator of transcription (Tat) protein. Cocaine abuse increases the incidence of HAND and exacerbates its severity by enhancing viral replication. Perturbation of dopaminergic transmission has been implicated as a risk factor of HAND. The presynaptic dopamine (DA) transporter (DAT) is essential for DA homeostasis and dopaminergic modulation of the brain function including cognition. Tat and cocaine synergistically elevate synaptic DA levels by acting directly on human DAT (hDAT), ultimately leading to dysregulation of DA transmission. Through integrated computational modeling and experimental validation, key residues have been identified in hDAT that play a critical role in Tat-induced inhibition of DAT and induce transporter conformational transitions. This review presents current information regarding neurological changes in DAT-mediated dopaminergic system associated with HIV infection, DAT-mediated adaptive responses to Tat as well as allosteric modulatory effects of novel compounds on hDAT. Understanding the molecular mechanisms by which Tat induces DAT-mediated dysregulation of DA system is of great clinical interest for identifying new targets for an early therapeutic intervention for HAND.

Original languageEnglish
Pages (from-to)78-89
Number of pages12
JournalPharmacology and Therapeutics
StatePublished - Mar 2018

Bibliographical note

Publisher Copyright:
© 2017 Elsevier Inc.


  • Allosteric modulator
  • Cocaine
  • Dopamine transporter
  • HIV-1 Tat
  • Mutation

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


Dive into the research topics of 'The role of human dopamine transporter in NeuroAIDS'. Together they form a unique fingerprint.

Cite this