HIV-associated sensory polyneuropathy and neuronal injury are associated with miRNA–455-3p induction

Asahchop, Eugene L.; Branton, William G.; Krishnan, Anand; Chen, Patricia; Yang, Dong; Kong, Linglong; Zochodne, Douglas W.; Brew, Bruce J.; Gill, M John; Power, Christopher

doi:10.1172/jci.insight.122450

Cited by 28 publications

(17 citation statements)

References 61 publications

(61 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This pathological pathway was also observed in neurons exposed to conditioned media derived from HIV-1-infected cells (Darbinian et al, 2008;Darbinian-Sarkissian et al, 2006;Peruzzi, Gordon, Darbinian, & Amini, 2002). Overall, these observations ascribe a role for Tat in reducing the expression and the kinase activity of the p35 complex that affects many key neuronal proteins, then (Asahchop et al, 2018). At last, daily intracerebroventricular administrations of the recombinant protein gp120…”

Section: Nerve Growth Factormentioning

confidence: 65%

“…NGF is a target gene of miRNA‐455‐3p, thus suggesting another impact of HIV‐1 infection on NGF signaling. Human neurons transfected with this miRNA also show reduced NGF expression and neurite outgrowth (Asahchop et al, 2018). At last, daily intracerebroventricular administrations of the recombinant protein gp120 in rats affect the expression of NGF and is associated with cortical cell death, but without relevant damage into the hippocampus (Bagetta et al, 1996).…”

Section: Neurotrophic Factors and Their Interactions With Hiv‐1mentioning

confidence: 99%

See 1 more Smart Citation

The delicate balance between neurotoxicity and neuroprotection in the context of HIV‐1 infection

Sénécal

Barat

Tremblay

2020

Glia

View full text Add to dashboard Cite

Human immunodeficiency virus type-1 (HIV-1) causes a spectrum of neurological impairments, termed HIV-associated neurocognitive disorder (HAND), following the infiltration of infected cells into the brain. Even though the implementation of antiretroviral therapy reduced the systemic viral load, the prevalence of HAND remains unchanged and infected patients develop persisting neurological disturbances affecting their quality of life. As a result, HAND have gained importance in basic and clinical researches, warranting the need of developing new adjunctive treatments. Nonetheless, a better understanding of the molecular and cellular mechanisms remains necessary. Several studies consolidated their efforts into elucidating the neurotoxic signaling leading to HAND including the deleterious actions of HIV-1 viral proteins and inflammatory mediators. However, the scope of these studies is not sufficient to address all the complexity related to HAND development. Fewer studies focused on an altered neuroprotective capacity of the brain to respond to HIV-1 infection. Neurotrophic factors are endogenous polyproteins involved in neuronal survival, synaptic plasticity, and neurogenesis. Any defects in the processing or production of these crucial factors might compose a risk factor rendering the brain more vulnerable to neuronal damages. Due to their essential roles, they have been investigated for their diverse interplays with HIV-1 infection. In this review, we present a complete description of the neurotrophic factors involved in HAND. We discuss emerging concepts for their therapeutic applications and summarize the complex mechanisms that down-regulate their production in favor of a neurotoxic environment. For certain factors, we finally address opposing roles that rather lead to increased inflammation.

show abstract

Section: Nerve Growth Factormentioning

confidence: 65%

Section: Neurotrophic Factors and Their Interactions With Hiv‐1mentioning

confidence: 99%

The delicate balance between neurotoxicity and neuroprotection in the context of HIV‐1 infection

Sénécal

Barat

Tremblay

2020

Glia

View full text Add to dashboard Cite

show abstract

“…This condition leads to neuropathic pain and is associated with substantial comorbidities and increased health care costs. Plasma miRNA profiles show differences between HIV patients with and without sDSP, and several miRNA biomarkers are reported to be associated with the presence of sDSP in HIV patients (see [ 30 ]). The corresponding binary classification problem was analyzed in [ 30 ] using random forest classifiers.…”

Section: Numerical Analysismentioning

confidence: 99%

“…Plasma miRNA profiles show differences between HIV patients with and without sDSP, and several miRNA biomarkers are reported to be associated with the presence of sDSP in HIV patients (see [ 30 ]). The corresponding binary classification problem was analyzed in [ 30 ] using random forest classifiers. However, the HIV data set can be further classified into four classes.…”

Section: Numerical Analysismentioning

confidence: 99%

Sparse Multicategory Generalized Distance Weighted Discrimination in Ultra-High Dimensions

Wang

Liu

et al. 2020

Entropy

Self Cite

View full text Add to dashboard Cite

Distance weighted discrimination (DWD) is an appealing classification method that is capable of overcoming data piling problems in high-dimensional settings. Especially when various sparsity structures are assumed in these settings, variable selection in multicategory classification poses great challenges. In this paper, we propose a multicategory generalized DWD (MgDWD) method that maintains intrinsic variable group structures during selection using a sparse group lasso penalty. Theoretically, we derive minimizer uniqueness for the penalized MgDWD loss function and consistency properties for the proposed classifier. We further develop an efficient algorithm based on the proximal operator to solve the optimization problem. The performance of MgDWD is evaluated using finite sample simulations and miRNA data from an HIV study.

show abstract

“…This database has a large number of participants with multimodal imaging data acquired using homogeneous hardware and software (Elliott et al, 2018). With the large number of participants in the UKB database, we have the opportunity to use the same database to discover and validate the findings independently, instead of adopting the ensemble methods to stabilize and validate the findings using the discovery set alone (Asahchop et al, 2018; Tu et al, 2020). Several GWAS of brain imaging based phenotypes have been reported (Elliott et al, 2018; Zhao et al, 2019) to take advantage of this large and rich database, but, a study of brain connectivity has not been conducted to the best of our knowledge.…”

Section: Introductionmentioning

confidence: 99%

Super‐variants identification for brain connectivity

Wang

et al. 2020

Human Brain Mapping

View full text Add to dashboard Cite

Identifying genetic biomarkers for brain connectivity helps us understand genetic effects on brain function. The unique and important challenge in detecting associations between brain connectivity and genetic variants is that the phenotype is a matrix rather than a scalar. We study a new concept of super‐variant for genetic association detection. Similar to but different from the classic concept of gene, a super‐variant is a combination of alleles in multiple loci but contributing loci can be anywhere in the genome. We hypothesize that the super‐variants are easier to detect and more reliable to reproduce in their associations with brain connectivity. By applying a novel ranking and aggregation method to the UK Biobank databases, we discovered and verified several replicable super‐variants. Specifically, we investigate a discovery set with 16,421 subjects and a verification set with 2,882 subjects, where they are formed according to release date, and the verification set is used to validate the genetic associations from the discovery phase. We identified 12 replicable super‐variants on Chromosomes 1, 3, 7, 8, 9, 10, 12, 15, 16, 18, and 19. These verified super‐variants contain single nucleotide polymorphisms that locate in 14 genes which have been reported to have association with brain structure and function, and/or neurodevelopmental and neurodegenerative disorders in the literature. We also identified novel loci in genes RSPO2 and TMEM74 which may be upregulated in brain issues. These findings demonstrate the validity of the super‐variants and its capability of unifying existing results as well as discovering novel and replicable results.

show abstract

HIV-associated sensory polyneuropathy and neuronal injury are associated with miRNA–455-3p induction

Cited by 28 publications

References 61 publications

The delicate balance between neurotoxicity and neuroprotection in the context of HIV‐1 infection

The delicate balance between neurotoxicity and neuroprotection in the context of HIV‐1 infection

Sparse Multicategory Generalized Distance Weighted Discrimination in Ultra-High Dimensions

Super‐variants identification for brain connectivity

Contact Info

Product

Resources

About