Functional Proteomics Reveal Unique Insights into Neuroinflammation (Part 1)

In recognition of Alzheimer’s & Brain awareness month, we are kicking off June with a blog series around the importance of understanding neuroinflammation in neurodegenerative disorders, associated challenges and how single cell proteomic technology can help.

Neurodegenerative diseases are a major threat to aging populations, affecting millions of people around the globe. Encompassing many conditions in which central nervous system cells cease to function, the most common is Alzheimer’s disease – it is estimated that approximately 44 million people worldwide are living with the disorder and that statistic is growing at an exponential rate.1,2,3

While treatments can help ease symptoms, there is no cure. What’s more, these disorders lack effective intervention strategies. The development of biomarkers is critical to not only improve early diagnosis, but to monitor disease progression, measure patient response to treatment and establish new therapeutic strategies.2

What we do know is that neuroinflammation plays an important role in neurodegenerative diseases, such as Alzheimer’s. As a complex biological response to nervous tissue injury involving many inflammatory mediators, adaptive and innate immune cells have been shown to penetrate the blood-brain barrier and are capable of releasing multiple inflammatory mediators that can result in nervous system (CNS) damage.2-8

For Alzheimer’s disease specifically, pro-inflammatory cytokines can impact amyloid precursor protein (APP) processes, β-amyloid aggregation, and TAU phosphorylation9—all neuropathological hallmarks of Alzheimer’s disease.

However, with a cure for Alzheimer’s disease remaining elusive, it is imperative for researchers to have access to more data. This has led them to studying functional proteomic technology in order to gain novel insights into the drivers of neuroinflammation.

A Shift in Proteomics

Neuronal deterioration is a hallmark sign of neurodegenerative disorders. Such deterioration results in changes in neuronal proteins, which is how most patients are diagnosed. To prevent further damage, early diagnosis is necessary. And in order to diagnose early on, proteins and their functions in the disease state must be examined.10 This is why recent breakthroughs in proteomics have aided researchers in the advancement of their work and now begin to shift their focus to functional analysis.

There are a multitude of proteomics approaches used to analyze protein expression, for monitoring cellular activities and for gaining a better understanding of biochemical pathways.11 Combined, these methods are transforming how diseases are studied as they allow for precise and large-scale protein analysis, helping researchers gain more knowledge of how diseases progress.2,11

Traditional Techniques Present Challenges in Assessing Neuroinflammation

In addition, for clinical trials, these types of bulk techniques make it harder to profile responders vs. nonresponders, which can hinder drug efficacy analyses. Understanding which specific cytokines are produced by each heterogeneous immune cells is important – and cellular functional phenotyping can reveal these cellular differences.2

By looking at single cell polyfunctionality, researchers can better characterize drivers of neuroinflammation. Assessing unique cytokine signatures of cellular subsets better defines relevant biomarkers of Alzheimer’s disease. One way to accomplish this is through the use of single cell functional proteomics, which enable patient stratification based on cellular functionality and biomarker expression to better predict therapeutic response.12

A Solution: IsoPlexis Single-Cell Secretome

To meet these challenges, IsoPlexis has developed a technology that is able to phenotype each immune cell by its extracellular function. We call this functional phenotyping.

With our breakthrough Single-Cell Secretome Solutions, users can analyze secreted cytokines directly from each single cell, across thousands of single cells in parallel, for the first time. The leap over existing technologies, like mass spectrometry and flow cytometry, is the Single-Cell Secretome solution’s ability to quantify and highly multiplex 32+ analytes simultaneously from each cell, and thus detect critical signatures in rare cells and cell subsets.13

Summary

While the race to discover a cure for all neurodegenerative diseases, including Alzheimer’s, persists, it is evident that the advancements being made in functional proteomics are helping to make the path a little easier. The ability to study proteins at a single cell level has revealed unique insights into neuroinflammation, allowing researchers to advance research more quickly. It’s only a matter of time before a cure is found.

Be sure to look for Part 2 of our series in which we examine applications that require a single-cell proteome solution, and download our Application Note on Neuroinflammation to learn more.

 

References

  1. Naqvi, E. (2017, June 30). Alzheimer’s Disease Statistics. Alzheimer’s News Today. https://alzheimersnewstoday.com/alzheimers-disease-statistics/#:~:text=It%20is%20estimated%20that%20there,all%20ages%20have%20Alzheimer’s%20diseas/
  2. Pal R, et. al. New insight into neurodegeneration: the role of proteomics. Molecular neurobiology. https://pubmed.ncbi.nlm.nih.gov/24323427/
  3. NCI Dictionary of Cancer Terms. National Cancer Institute https://www.cancer.gov/publications/dictionaries/cancer-terms/def/neurodegenerative-disorder
  4. Town, T., Nikolic, V. & Tan, J. The microglial “activation” continuum: from innate to adaptive responses. J Neuroinflammation 2, 24, doi:10.1186/1742-2094-2-24 (2005).
  5. Akiyama, H. et al. Inflammation and Alzheimer’s disease. Neurobiol Aging 21, 383-421 (2000).
  6. Kim, Y. S. & Joh, T. H. Microglia, major player in the brain inflammation: their roles in the pathogenesis of Parkinson’s disease. Exp Mol Med 38, 333-347, doi:10.1038/emm.2006.40 (2006).
  7. Dheen, S. T., Kaur, C. & Ling, E. A. Microglial activation and its implications in the brain diseases. Curr Med Chem 14, 1189-1197 (2007).
  8. Town, T. Alternative Abeta immunotherapy approaches for Alzheimer’s disease. CNS Neurol Disord Drug Targets 8, 114-127 (2009).
  9. Domingues, C., da Cruz E Silva, O., & Henriques, A. G. (2017). Impact of Cytokines and Chemokines on Alzheimer’s Disease Neuropathological Hallmarks. Current Alzheimer research, 14(8), 870–882. https://doi.org/10.2174/1567205014666170317113606
  10. Puranik N, et. al. Proteomics and Neurodegenerative Disorders: Advancements in the Diagnostic Analysis. Current protein & peptide science. https://pubmed.ncbi.nlm.nih.gov/32392110/
  11. Single Cell Proteomics: Each Cell Makes a Difference. IsoPlexis. http://www.isoplexis.com/
  12. https://isoplexis.com/literature/isoplexis-proteomic-product-suite-for-neuroinflammation/
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