Transcriptomics Study of Neurodegenerative Disease: Emphasis on Synaptic Dysfunction Mechanism in Alzheimer's Disease

Author(s): Sajjad Karim , Zeenat Mirza , Shakeel A. Ansari , Mahmood Rasool , Zafar Iqbal , Sayed S. Sohrab , Mohammad A. Kamal , Adel M. Abuzenadah , Mohammed H. Al-Qahtani .

Journal Name: CNS & Neurological Disorders - Drug Targets

Volume 13 , Issue 7 , 2014

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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.

Keywords: Alzheimer's disease, canonical pathways, microarray, neurodegenerative diseases, synaptic dysfunction, transcriptomics.

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Article Details

VOLUME: 13
ISSUE: 7
Year: 2014
Page: [1202 - 1212]
Pages: 11
DOI: 10.2174/1871527313666140917113446
Price: $58

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