Why do we lose it? Analytical insights into human neuromuscular degeneration
Dr. Jonas Bergquist
Department of Chemistry
Friday, February 28, 2014
C2-361 (Reading Room)
Abstract: No matter what we do, eat or practice – sooner or later we all will start losing our abilities to control our bodily functions, maintain muscle control and innervations. Most of us will grow old and degrade by natural causes, while some of us unfortunately will be affected by fast or slow progressive diseases or even have accidents with traumas that will initiate dramatic degenerative effects. Amyotrophic lateral sclerosis (ALS) is the most common type of motor neuron disease in adult patients and is characterized by progressive muscle paralysis. However, the clinical tools for ALS diagnostics do not perform well enough and their improvement is needed. We have recently demonstrated that a shotgun proteomic approach coupled with relative quantitative dimethyl labeling (DML) method can analyze the global changes in the human skeletal muscle proteome from ALS patients. Very limited amount of muscle biopsy taken from randomized ALS patients and healthy controls were used for comparison. The underlying objective of our study was to identify potential protein biomarkers related to the development of ALS but also to be able to get in detail structural characteristics of protein modifications that are initiated by disease. These proteins are involved in several biological processes including muscle development and contraction, metabolic process, enzyme activity, glycolysis, regulation of apoptosis and transport activity. In order to eliminate a risk to confuse ALS with other denervation, muscle biopsies of patients with postpolio syndrome and Charcot-Marie-Tooth disease (negative controls) were compared to those of ALS and control samples. In parallel we have been monitoring patients from the intensive care unit (ICU) that after accidents and trauma ends up in assisted ventilation or respirator treatment. These patients experience dramatic muscle denervation and degeneration already after a few days of treatment. We have identified a number of different factors behind this phenomenon that also reveals new knowledge about the natural aging muscle.