title: Transcriptomics study of neurodegenerative disease: emphasis on synaptic dysfunction mechanism in Alzheimer's disease.
abstract: Alzheimer's disease (AD) is a common neurodegenerative disorder primarily affecting memory and thinking ability; caused by progressive degeneration and death of nerve cells. In this study, we integrated multiple dataset retrieved from the National Center for Biotechnology Information's Gene Expression Omnibus database, and took a systems-biology approach to compare and distinguish the molecular network based synaptic dysregulation associated with AD in particular and neurodegenerative diseases in general. We first identified 832 differentially expressed genes using cut off P value <0.5 and fold change > 2, followed by gene ontology study to identify genes associated with synapse (n=95) [membrane associated guanylate kinase, 2, amyloid beta precursor protein, neurotrophic tyrosine kinase, receptor, type 2], synapse part [γ-aminobutyric acid A receptor, γ1], synaptic vesicle [glutamate receptor, ionotropic, α-amino-3-hydroxy-5- methyl-4-isoxazole propionic acid receptor 2, synaptoporin], pre- and post-synaptic density [neuronal calcium sensor 1, glutamate receptor, metabotropic 3]. We integrated these data with known pathways using Ingenuity Pathway Analysis tool and found following synapse associated pathways to be most affected; γ-aminobutyric acid receptor signaling, synaptic long term potentiation/depression, nuclear factor-erythroid 2-related factor 2-mediated oxidative stress response, huntington's disease signaling and Reelin signaling in neurons. In conclusion, synaptic dysfunction is tightly associated with the development and progression of neurodegenerative diseases like AD.
authors.forename: Sajjad
authors.initials: S
authors.lastname: Karim
authors.forename: Zeenat
authors.initials: Z
authors.lastname: Mirza
authors.forename: Shakeel A
authors.initials: SA
authors.lastname: Ansari
authors.forename: Mahmood
authors.initials: M
authors.lastname: Rasool
authors.forename: Zafar
authors.initials: Z
authors.lastname: Iqbal
authors.forename: Sayed S
authors.initials: SS
authors.lastname: Sohrab
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Kamal
authors.forename: Adel M
authors.initials: AM
authors.lastname: Abuzenadah
authors.affiliation: King Fahd Medical Research Center, PO Box-80216, King Abdulaziz University, Jeddah -21589, Saudi Arabia. zmirza1@kau.edu.sa.
authors.forename: Mohammed H
authors.initials: MH
authors.lastname: Al-Qahtani
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D030541:Databases, Genetic; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D017774:Long-Term Potentiation / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018079:Receptors, GABA / Q000378:metabolism; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D018079:Receptors, GABA; D000091042:Reelin Protein; C000717127:RELN protein, human; D012697:Serine Endopeptidases