Abstract
The neurological complications of AIDS (neuroAIDS) during the infection of human immunodeficiency virus (HIV) are symptomized by non-specific, multifaceted neurological conditions and therefore, defining a specific diagnosis/treatment mechanism(s) for this neuro-complexity at the molecular level remains elusive. Using an in silico based integrated gene network analysis we discovered that HIV infection shares convergent gene networks with each of twelve neurological disorders selected in this study. Importantly, a common gene network was identified among HIV infection, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and age macular degeneration. An mRNA microarray analysis in HIV-infected monocytes showed significant changes in the expression of several genes of this in silico derived common pathway which suggests the possible physiological relevance of this gene-circuit in driving neuroAIDS condition. Further, this unique gene network was compared with another in silico derived novel, convergent gene network which is shared by seven major neurological disorders (Alzheimer’s disease, Parkinson’s disease, Multiple Sclerosis, Age Macular Degeneration, Amyotrophic Lateral Sclerosis, Vascular Dementia, and Restless Leg Syndrome). These networks differed in their gene circuits; however, in large, they involved innate immunity signaling pathways, which suggests commonalities in the immunological basis of different neuropathogenesis. The common gene circuits reported here can provide a prospective platform to understand how gene-circuits belonging to other neuro-disorders may be convoluted during real-time neuroAIDS condition and it may elucidate the underlying–and so far unknown–genetic overlap between HIV infection and neuroAIDS risk. Also, it may lead to a new paradigm in understanding disease progression, identifying biomarkers, and developing therapies.
Highlights
The clinicopathological characteristics of different neurological disorders are often indistinguishable
Multiple sclerosis showed the highest number of shared genes with AIDS, followed by age macular degeneration, Alzheimer’s disease, autism-autism spectrum, and so on
The challenge is to dissect the molecular networks and dysregulated pathways shared between neuroAIDS and different neurological disorders
Summary
The clinicopathological characteristics of different neurological disorders are often indistinguishable. Symptoms such as hallucinations, memory loss, dementia, and other psychotic symptoms are common to almost all neuro-disorders. A correlation at the interface of neurobiology and human genetics is being drawn with the discovery of multiple genetic signatures belonging to a single disease or common to various neuro-disorders. Disrupted expression of even a single gene possesses the ability to affect several molecular pathways and multiple psychotic phenotypes may have connection in converged molecular circuits. The discovery of shared dysregulated molecular pathways among various neuro-disorders can accelerate mechanistic studies of their pathophysiology which, in turn, can lead to appropriate therapies
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