MALDI imaging of post‐mortem human spinal cord in amyotrophic lateral sclerosis |
| |
Authors: | Jörg Hanrieder Titti Ekegren Malin Andersson Jonas Bergquist |
| |
Institution: | 1. Department of Chemical and Biological Engineering, Analytical Chemistry, Chalmers University of Technology, , Gothenburg, Sweden;2. Department of Chemistry, Biomedical Center, Analytical Chemistry and Science for Life Laboratory, Uppsala University, , Uppsala, Sweden;3. Department of Pharmaceutical Biosciences, Drug Safety and Toxicology, Uppsala University, , Uppsala, Sweden;4. Department of Neuroscience, Neurology, Uppsala University Hospital, , Uppsala, Sweden |
| |
Abstract: | Amyotrophic lateral sclerosis (ALS) is a devastating, rapidly progressing disease of the central nervous system that is characterized by motor neuron degeneration in the brainstem and the spinal cord. Matrix‐assisted laser desorption/ionization (MALDI) imaging mass spectrometry is an emerging powerful technique that allows for spatially resolved, comprehensive, and specific characterization of molecular species in situ. In this study, we report for the first time the MALDI imaging‐based spatial protein profiling and relative quantification of post‐mortem human spinal cord samples obtained from ALS patients and controls. In normal spinal cord, protein distribution patterns were well in line with histological features. For example, thymosin beta 4, ubiquitin, histone proteins, acyl‐CoA‐binding protein, and macrophage inhibitory factor were predominantly localized to the gray matter. Furthermore, unsupervised statistics revealed a significant reduction of two protein species in ALS gray matter. One of these proteins (m/z 8451) corresponds to an endogenous truncated form of ubiquitin (Ubc 1–76), with both C‐terminal glycine residues removed (Ubc‐T/Ubc 1–74). This region‐specific ubiquitin processing suggests a disease‐related change in protease activity. These results highlight the importance of MALDI mass spectrometry as a versatile approach to elucidate molecular mechanisms of neurodegenerative diseases. |
| |
Keywords: | amyotrophic lateral sclerosis imaging mass spectrometry matrix‐assisted laser desorption/ionization post‐mortem spinal cord tissue imaging |
|
|