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academies
August 23-24, 2018 | Paris, France
Neurology and Neurological Disorders
18
th
International Conference on
Journal of Neurology and Neurorehabilitation Research | Volume 3
M
utations causing the most common form of early onset
dementia, frontotemporal dementia, have been identified,
but the subsequent disease mechanisms are not well understood.
Rather than focusing on a priori selected genes, we apply a
multi-stage, systems biology approach, reasoning that defining
transcriptional networks would significantly advance mechanistic
understanding. By taking genetic background into consideration,
representing a variety of causal mutations in our transcriptomic
analyses, coupled with gene co-expression network analysis, and
validation inadozen independentdatasets,webridgedthespecies
divide and identify disease-relevant gene networks representing
specific molecular pathways. These networks are dysregulated
not only across a variety of FTD mouse models involving different
mutations and genetic backgrounds, but also in FTD patient iPSC-
lines and more importantly, post mortem human samples. We
further validate network predictions via proteomic studies in
human brain and show that a hub of a putative regulatory miRNA
module, miR-203, re-capitulates mRNA co-expression patterns
associated with disease state and induces neuronal cell death.
Moreover, we use disease-associated co-expression modules to
identify probe compounds and show that they have the predicted
protective effect. Collectively, we identify conserved, disease
relevant co-expression networks representing convergent changes
in dementia, and validate miR-203 as a novel regulator of core
network components and neurodegeneration.
Speaker Biography
Vivek Swarup completed his PhD from Laval University, Quebec, Canada. He is the
assistant professor at the Department of Neurobiology and Behavior, University of
California, Irvine, USA. He has over 20 publications that have been cited over 1100
times, and his publication H-index is 15.
e:
vswarup@uci.eduVivek Swarup
University of California, USA
Identification of evolutionarily conserved gene networks mediating
Neurodegenerative Dementia