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microRNA (miRNA)-Mediated Pathogenetic Signaling in Alzheimer’s Disease (AD)

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Abstract

Alzheimer’s disease (AD) is an expanding health and socioeconomic concern in industrialized societies, and the leading cause of intellectual impairment in our aging population. The cause of AD remains unknown, and there are currently no effective treatments to stop or reverse the progression of this uniquely human and age-related neurological disorder. Elucidation of the AD mechanism and factors that contribute to the initiation, progression, and spreading of this chronic and fatal neurodegeneration will ultimately result in improved and effective diagnostics and therapeutic strategies.

microRNAs (miRNAs) comprise a relatively recently discovered category of 20–24 nucleotide non-coding RNAs that function post-transcriptionally in shaping the transcriptome of the cell, and in doing so, contribute to the molecular-genetics and phenotype of human CNS health and disease. To date about 2550 unique mature human miRNAs have been characterized, however only highly selected miRNA populations appear to be enriched in different anatomical compartments within the CNS.

This general commentary for the ‘Special Issue: 40th Year of Neurochemical Research’ will bring into perspective (i) some very recent findings on the extraordinary biophysics and signaling properties of CNS miRNA in AD and aging human brain; (ii) how specific intrinsic biophysical attributes of miRNAs may play defining roles in the establishment, proliferation and spreading of the AD phenotype; and (iii) how miRNAs can serve as prospective therapeutic targets and biomarkers potentially useful in the clinical management of this terminal neurological disease whose incidence in our rapidly aging population is reaching epidemic proportions.

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Acknowledgments

Sincere thanks are extended to Drs. L. Carver, E. Head, W. Poon, H. LeBlanc, F. Culicchia, C. Eicken and C. Hebel for short post-mortem interval (PMI) human brain and/or retinal tissues or extracts, miRNA array work and initial data interpretation, and to D Guillot and AI Pogue for expert technical assistance. Thanks are also extended to the many neuropathologists, physicians and researchers of Canada and the US who have provided high quality, short post-mortem interval (PMI) human CNS and retinal tissues or extracted brain and retinal total and fractionated RNA for scientific study. Research on miRNA in the Lukiw laboratory involving the innate-immune response in AD, AMD and in other forms of neurological or retinal disease, amyloidogenesis and neuro-inflammation was supported through an unrestricted grant to the LSU Eye Center from Research to Prevent Blindness (RPB); the Louisiana Biotechnology Research Network (LBRN) and NIH Grants NEI EY006311, NIA AG18031 and NIA AG038834.

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Correspondence to Walter J. Lukiw.

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This work was presented in part at the Society for Neuroscience (SFN) Annual Meeting 15–19 November 2014, Washington, USA and at the Association for Research in Vision and Ophthalmology (ARVO) Annual conference 3–7 May 2015 in Denver CO USA.

Special Issue: 40th Year of Neurochemical Research.

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Hill, J.M., Lukiw, W.J. microRNA (miRNA)-Mediated Pathogenetic Signaling in Alzheimer’s Disease (AD). Neurochem Res 41, 96–100 (2016). https://doi.org/10.1007/s11064-015-1734-7

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  • DOI: https://doi.org/10.1007/s11064-015-1734-7

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