Prognostic value of serum/plasma neurofilament light chain for COVID-19-associated mortality.

Objective: Given the continued spread of coronavirus 2, the early predictors of coronavirus disease 19 (COVID-19) associated mortality might improve patients' outcomes. Increased levels of circulating neurofilament light chain (NfL), a biomarker of neuronal injury, have been observed in severe COVID-19 patients. We investigated whether NfL provides non-redundant clinical value to previously identified predictors of COVID-19 mortality.

Prognostic Value of Serum/Plasma Neurofilament Light Chain for COVID-19 Associated Mortality.

Given the continued spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), early predictors of coronavirus disease 19 (COVID-19) mortality might improve patients’ outcomes. Increased levels of circulating neurofilament light chain (NfL), a biomarker of neuro-axonal injury, have been observed in patients with severe COVID-19. We investigated whether NfL provides non-redundant clinical value to previously identified predictors of COVID-19 mortality.

Neurofilament light chain levels correlate with clinical measures in CLN3 disease.

Purpose: CLN3 disease is a neurodegenerative disorder with onset in childhood. It affects multiple functions at different developmental stages. Incomplete understanding of the pathophysiology hampers identification of cell and tissue biochemical compounds reflective of the disease process.

Productive infection of human neural progenitor cells by R5 tropic HIV-1: opiate co-exposure heightens infectivity and functional vulnerability.

Objective: HIV type-1 (HIV-1) causes a spectrum of central nervous system (CNS) complications; many are worsened by opiate co-exposure. Human neural progenitor cells (hNPCs) give rise to all CNS neurons and macroglia. We tested the hypothesis that hNPC maturation and fate are altered by HIV and opiates, contributing to HIV-1-related neuropathology.

Exploration of bivalent ligands targeting putative mu opioid receptor and chemokine receptor CCR5 dimerization.

Modern antiretroviral therapies have provided HIV-1 infected patients longer lifespans and better quality of life. However, several neurological complications are now being seen in these patients due to HIV-1 associated injury of neurons by infected microglia and astrocytes. In addition, these effects can be further exacerbated with opiate use and abuse.

Chronic HIV-1 Tat and HIV reduce Rbfox3/NeuN: evidence for sex-related effects.

The NeuN antibody has been widely used to identify and quantify neurons in normal and disease situations based on binding to a nuclear epitope in most types of neurons. This epitope was recently identified as the RNA-binding, feminizing locus on X-3 (Rbfox3), a member of the larger, mammalian Fox1 family of RNA binding proteins. Fox1 proteins recognize a unique UGCAUG mRNA motif and regulate alternative splicing of precursor mRNA to control post-transcriptional events important in neuronal differentiation and central nervous system development.

GSK3β-activation is a point of convergence for HIV-1 and opiate-mediated interactive neurotoxicity.

Infection of the CNS with HIV-1 occurs rapidly after primary peripheral infection. HIV-1 can induce a wide range of neurological deficits, collectively known as HIV-1-associated neurocognitive disorders. Our previous work has shown that the selected neurotoxic effects induced by individual viral proteins, Tat and gp120, and by HIV(+) supernatant are enhanced by co-exposure to morphine.

HIV-1 and morphine regulation of autophagy in microglia: limited interactions in the context of HIV-1 infection and opioid abuse.

Unlabelled: Microglia are the predominant resident central nervous system (CNS) cell type productively infected by HIV-1, and play a key role in the progression of HIV-associated dementia (HAD). Moreover, neural dysfunction and progression to HAD are accelerated in opiate drug abusers. In the present study, we examined the role of the autophagy pathway in the neuropathogenesis of HIV-1 using primary human microglial cells and determined whether opiates converge at this point.

Morphine enhances HIV-1SF162-mediated neuron death and delays recovery of injured neurites.

HIV-1 enters the CNS soon after initial systemic infection; within the CNS parenchyma infected and/or activated perivascular macrophages, microglia and astrocytes release viral and cellular toxins that drive secondary toxicity in neurons and other cell types. Our previous work has largely modeled HIV-neuropathology using the individual viral proteins Tat or gp120, with murine striatal neurons as targets. To model disease processes more closely, the current study uses supernatant from HIV-1-infected cells.