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Shared mechanisms among neurodegenerative diseases: from genetic factors to gene networks

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Abstract

Neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis are pressing health concerns in modern societies for which effective therapies are still lacking. Recent high-throughput genomic technologies have enabled genome-scale, multidimensional investigations to facilitate a better understanding of the underlying mechanisms and the identification of novel targets. Here we review the molecular insights gained through such studies, and compare the similarities and differences between neurodegenerative diseases revealed by systems genomics and gene network modelling approaches. We focus specifically on the shared mechanisms at multiple molecular scales ranging from genetic factors to gene expression to network-level features of gene regulation, and whenever possible also point out mechanisms that distinguish one disease from another. Our review sets the stage for similar genomewide inspection in the future on shared/distinct features of neurodegenerative diseases at the levels of cellular, proteomic or epigenomic signatures, and how these features may interact to determine the progression and treatment response of different diseases afflicting the same individual.

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Acknowledgements

This work was partially supported by the Intramural Programme of NIAID (National Institute of Allergy and Infectious Diseases) at the National Institutes of Health (NIH) to MN, NIH grants DK104363 and NS103088 to XY, and UCLA Hyde Fellowship to DA.

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Correspondence to Xia Yang or Manikandan Narayanan.

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Arneson, D., Zhang, Y., Yang, X. et al. Shared mechanisms among neurodegenerative diseases: from genetic factors to gene networks. J Genet 97, 795–806 (2018). https://doi.org/10.1007/s12041-018-0963-3

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