Title:Transcriptomics Study of Neurodegenerative Disease: Emphasis on Synaptic Dysfunction Mechanism in Alzheimer's Disease
Volume: 13
Issue: 7
Author(s): Sajjad Karim, Zeenat Mirza, Shakeel A. Ansari, Mahmood Rasool, Zafar Iqbal, Sayed S. Sohrab, Mohammad A. Kamal, Adel M. Abuzenadah and Mohammed H. Al-Qahtani
Affiliation:
Keywords:
Alzheimer's disease, canonical pathways, microarray, neurodegenerative diseases, synaptic dysfunction,
transcriptomics.
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 systemsbiology
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.
