MALDI Imaging of Post Mortem Human Spinal Cord in Amyotrophic Lateral Sclerosis

• Amyotrophic lateral sclerosis (ALS) is a devastating, rapidly progressing disease of the central nervous system that is characterized by motor neuron degeneration in the brain stem and the spinal cord. Matrix assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) 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, 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 grey matter. Furthermore, unsupervised statistics revealed a significant reduction of two protein species in ALS grey 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 IMS as a versatile approach to elucidate molecular mechanisms of neurodegenerative diseases.

Ämnesord

NATURVETENSKAP  -- Kemi (hsv//swe)

NATURAL SCIENCES  -- Chemical Sciences (hsv//eng)

Nyckelord

amyotrophic lateral sclerosis

imaging mass spectrometry

matrix-assisted laser desorption/ionization

post-mortem spinal cord

tissue imaging.

Biokemi

Biochemistry

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)