Shared Molecular Signatures Across Neurodegenerative Diseases and Herpes Virus Infections Highlights Potential Mechanisms for Maladaptive Innate Immune Responses.
Ana Caroline Costa SaHeather MadsenJames R BrownPublished in: Scientific reports (2019)
Growing evidence suggests that peripheral factors to the brain driving neuro-inflammation could affect Alzheimer's Disease (AD) and Parkinson's Disease (PD) severity. Herpes simplex virus type 1 (HSV1) infection has been associated with AD while other related viruses, including cytomegalovirus (CMV), Epstein-Bar virus and human herpesvirus 6 (HHV6), are known to infect neurons. Here we compare gene expression profiles between AD or PD patients to those afflicted with herpes viral infections as to discover novel potential neuro-inflammation pathways. We found multiple significant differentially expressed genes (DEGs) shared between AD/PD and viral infections including SESN3 which has a genetic association for increased AD risk. Pathway enrichment analysis revealed viruses shared Oxidative Stress Defense System and LRRK2 pathways with AD and PD, respectively. We further processed our data to identify novel target and drug-repurposing opportunities including anti-inflammatory therapy, immune-modulators and cholinesterase inhibitors which could lead to new therapeutics paradigms for these neurodegenerative diseases.
Keyphrases
- herpes simplex virus
- oxidative stress
- immune response
- genome wide
- end stage renal disease
- sars cov
- small molecule
- anti inflammatory
- newly diagnosed
- endothelial cells
- chronic kidney disease
- stem cells
- gene expression
- dna methylation
- dendritic cells
- prognostic factors
- risk assessment
- machine learning
- spinal cord injury
- spinal cord
- emergency department
- peritoneal dialysis
- dna damage
- human health
- ischemia reperfusion injury
- single cell
- inflammatory response
- single molecule
- patient reported outcomes
- cognitive decline
- deep learning
- drug induced
- blood brain barrier
- resting state
- mild cognitive impairment
- artificial intelligence
- electronic health record
- epstein barr virus
- functional connectivity
- mesenchymal stem cells
- transcription factor
- replacement therapy
- patient reported
- heat shock
- disease virus