Researchers at the Cleveland Clinic have published their findings of a proteomic investigation of APBD that adds to our understanding of the disease’s underlying mechanism. The findings have been published in the scientific journal Frontiers in Neurology. Understanding the pathogenesis of ABPD is important for the development of effective APBD therapies.

The researchers, led by Dr. Marvin Natowicz (Professor of Pathology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, and a staff physician at the Cleveland Clinic), used lymphoblasts to explore the underlying mechanism of APBD. 

Lymphocytes, a type of white blood cell, were obtained from the blood of volunteers and then transformed in the laboratory to an immortalized form of lymphocytes called lymphoblasts. Lymphoblasts, in turn, are relatively easy to grow and use in different types of experiments. 

The investigators hypothesized that proteomic analysis of lymphocytes from GBE1-deficient individuals could serve as a useful tool to potentially provide insights into GBE1-mediated pathobiology. Until now, there has been limited data utilizing this experimental approach to study the biology of APBD. In this exploratory proteomic study, they quantified the diverse set of proteins of lymphoblasts from 3 individuals with APBD and 15 age- and gender-matched controls using a powerful mass spectrometry approach, and then validated their findings using an independent methodology.

The findings showed 531 differentially expressed proteins out of 3,427 detected between APBD subjects vs. controls, including the pronounced deficiency of glycogen branching enzyme, GBE1. Bioinformatic analyses of the proteomic data indicated multiple canonical pathways and protein-protein interaction networks to be disturbed in APBD subjects, including: RNA processing/transport/translation, cell cycle control/replication, mTOR signaling, protein ubiquitination, unfolded protein and endoplasmic reticulum stress responses, glycolysis, and cell death/apoptosis. 

Dr. Natowicz stated, “Our findings show that impairments in these processes are primary or secondary factors in the pathobiology of APBD and confirm several previously recognized pathophysiological processes. In addition, one unexpected and novel finding was a significant dysregulation of the translation of proteins. Given that dysregulation of translation is a major contributing factor to the pathogenesis of several neurodegenerative disorders, this new finding warrants further exploration”. 

“The lymphoblast proteomic assay could be used as an adjunctive follow-up approach to gauge if promising therapeutics normalize the abnormal proteins of APBD lymphoblasts,” added Dr. Natowicz.

Editor’s Note: Research Highlights is an ongoing feature in our newsletter. It is focused on scientific publications of interest to our community. Our thanks to Dr. Marvin Natowicz for sharing their research with us!