Opioid Modulation of Neuronal Iron and Potential Contributions to NeuroHIV

Part of the Methods in Molecular Biology book series (MIMB, volume 2201)


Opioid use has substantially increased over recent years and remains a major driver of new HIV infections worldwide. Clinical studies indicate that opioids may exacerbate the symptoms of HIV-associated neurocognitive disorders (HAND), but the mechanisms underlying opioid-induced cognitive decline remain obscure. We recently reported that the μ-opioid agonist morphine increased neuronal iron levels and levels of ferritin proteins that store iron, suggesting that opioids modulate neuronal iron homeostasis. Additionally, increased iron and ferritin heavy chain protein were necessary for morphine’s ability to reduce the density of thin and mushroom dendritic spines in cortical neurons, which are considered critical mediators of learning and memory, respectively. As altered iron homeostasis has been reported in HAND and related neurocognitive disorders like Alzheimer’s, Parkinson’s, and Huntington’s disease, understanding how opioids regulate neuronal iron metabolism may help identify novel drug targets in HAND with potential relevance to these other neurocognitive disorders. Here, we review the known mechanisms of opioid-mediated regulation of neuronal iron and corresponding cellular responses and discuss the implications of these findings for patients with HAND. Furthermore, we discuss a new molecular approach that can be used to understand if opioid modulation of iron affects the expression and processing of amyloid precursor protein and the contributions of this pathway to HAND.

Key words

Opioid Morphine Iron Endolysosome Ferritin Neuron Amyloid NeuroHIV HAND Chemokine 



Work supported by the National Institutes of Health (DA015014, DA032444, and DA040519 grants to OM).


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© Springer Science+Business Media, LLC, part of Springer Nature 2021

Authors and Affiliations

  1. 1.Department of Pharmacology & PhysiologyDrexel University College of MedicinePhiladelphiaUSA
  2. 2.Department of Pharmacy and BiotechnologyUniversity of BolognaBolognaItaly
  3. 3.Department of Microbiology & ImmunologyDrexel University College of MedicinePhiladelphiaUSA
  4. 4.Center for Neuroimmunology and CNS Therapeutics, Institute for Molecular Medicine and Infectious DiseaseDrexel University College of MedicinePhiladelphiaUSA

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