Trends in Neuroscience Research

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Neurodegenerative diseases represent a growing health concern and economic burden as the aging population increases. According to the World Health Organization's 2006 report on Neurological Disorders, the rates of Alzheimer's disease (AD) and other dementias are projected to increase by 66% between 2005 to 2030. These statistics serve as a call to action for the medical and research communities for new discoveries leading to insights into disease mechanisms, biomarker and therapeutic developments and improved diagnostic tests.

In recent years, the fields of neuroscience and clinical neurology have benefitted from advanced molecular techniques. NanoString's molecular barcoding technology is well-positioned to address the challenges faced by neurodegenerative disease researchers including limited and challenging sample types, data reproducibility, and data analysis. This is evidenced by the growing body of publications demonstrating the research utility of the nCounter® Analysis System to reveal biological insights across neurological disorders (Figure 1 in 'Publications' below and Figure 2).

Cell Press Supplement Pathological Mechanisms of Neurodegeneration

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Cell Press Selections

Read "Pathological Mechanisms of Neurodegeneration" in the Cell Press Supplement.

Cell Press Supplement Pathological Mechanisms of Neurodegeneration

Neuropathology Application Note

Read "Deciphering the Complexities of Neurodegeneration and Neuroinflammation" application note about gene expression.

 

New Insights into Neuroscience Research

Explore this publication review of top neuroscience studies to see how gene expression technology is reshaping research capabilities in neuroscience.

Neuropathology Application Note Insights into Neuroscience Research Using nCounter Technology

Pathway-based gene expression studies have proven valuable when studying complex diseases, both in providing a framework for comprehensive measurement of biological mechanisms and in establishing potentially prognostic and predictive signatures of disease progression and drug response. Recent gene expression studies have implicated biological pathways such as inflammation, protein homeostasis, RNA splicing, and mitochondrial fidelity as key in the development and progression of multiple neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and Alzheimer's disease (AD).

NanoString Technologies provides customizable panels that allow for the analysis of up to 800 RNA, DNA, or Protein targets, encompassing multiple pathways from a single sample. With limited sample types, particularly from human specimens, extracting the maximal amount of relevant information from each sample is critical. Researchers have demonstrated the power of the nCounter gene expression platform to generate robust results from CNS tissue, as well as peripheral blood and induced pluripotent stem cells.

Because the nCounter platform does not require amplification or the use of enzymes, challenging samples like post-mortem FFPE tissue can also be reliably analyzed to yield reproducible results. Moreover, NanoString offers solutions for single cell and low input samples aimed at getting the most biological information from the smallest sample. In contrast to other technologies that often require extended bioinformatics analysis, NanoString's simple digital read-outs and data analysis tools put the biological understanding back in the researcher's hand and serve to expedite the time from experimental design to discovery.

Given that many neurodegenerative diseases manifest pathologically as proteopathies, it is understandable that much emphasis has been placed on direct investigation of proteins. These studies have been key in understanding the mechanisms of protein aggregation and developing strategies to prevent, mitigate, and reverse aberrant protein accumulations in the nervous system. Thanks to genome-wide association studies, increasing numbers of disease causing genes are being identified allowing for investigation into function of corresponding mutant proteins, thus highlighting the importance of complementary genetic and biochemical analyses in the study of neurodegenerative disease pathogenesis. Many of these studies have uncovered additional roles for RNA processing and splicing, revealing another layer of dysfunction in neurodegeneration. Furthermore, the RNA processing defects and other pre-translational modes of regulation make the combined measurement of protein and RNA crucial, as the full understanding of disease at the molecular level requires all intermediates between genotype and phenotype.

NanoString has recently introduced 3D Biology™ assays which enable multi-analyte (i.e. RNA, DNA and Protein) multiplex analysis of key pathways in immune response and solid tumor progression (nanostring.com/3D). Future developments involve the ability to spatially resolve and simultaneously quantitate RNA and protein on a single platform, empowering a unique method for digital counting of both analytes from a single sample (nanostring.com/DSP).

Modern genomics technologies have advanced considerably in recent years and are proving critical in addressing the challenges of neurodegenerative disease diagnosis and research. Looking beyond disease diagnosis to disease management as new neurodegenerative disease treatments are tested and developed, there is an even greater need to understand various mechanisms of response or resistance to treatments. More robust technology and wide-spread accessibility has expanded the reach to an increasing number of scientists who are using gene expression profiling to better understand mechanisms of disease and treatment response. Gene expression profiling has the potential to support the next step forward in neurodegenerative research, allowing for the identification of biomarkers of disease that will allow for early diagnosis, classification of disease heterogeneity and ultimately, precision medicine on par with that currently available for cancer patients. NanoString has a mission to enable precision medicine through tranlsational research with active partnerships with the research community for the development of biomarkers and gene expression signatures.

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Butovsky O. et al., Targeting miR-155 restores abnormal microglia and attenuates disease in SOD1 mice.[Epub ahead of print]., Annals of Neurology, Nov 10, 2014 

Donnelly C.J. et al., RNA toxicity from the ALS/FTD C9ORF72 expansion is mitigated by antisense intervention.80(2):415-428, Neuron, Oct 16, 2013 

Liao M-C. et al., Single-Cell Detection of Secreted Aβ and sAPPα± from Human IPSC-Derived Neurons and Astrocytes.[Epub ahead of print]., J. Neuroscience, Feb 03, 2016 

Locascio J.J. et al., Association between α±-synuclein blood transcripts and early, neuroimaging-supported Parkinson՚s disease.[Epub ahead of print]., Brain, Jul 28, 2015 

Mayo L. et al., IL-10-dependent Tr1 cells attenuate astrocyte activation and ameliorate chronic central nervous system inflammation.[Epub ahead of print]., Brain, May 31, 2016 

Urup T. et al., Angiotensinogen and HLA class II predict bevacizumab response in recurrent glioblastoma patients., Molecular Oncology, May 26, 2016

Angiotensinogen and HLA class II predict Bevacizumab response in recurrent glioblastoma patients

Transcriptomic comparison of sorted mouse cells to establish microglia gene signatures

Analysis of iPSC’s to confirm C9ORF72 repeat expansion in ALS patients

Evaluation of α-synuclein gene transcripts in Parkinson’s disease patients using whole blood samples

CNS Poster- Deciphering the complexities of neurodegeneration and neuroinflammation with NanoString gene expression profiling

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