Linking neuron and skin: matrix metalloproteinases in amyotrophic lateral sclerosis (ALS)

J Neurol Sci. 2009 Oct 15;285(1-2):62-6. doi: 10.1016/j.jns.2009.05.025. Epub 2009 Jun 12.


Amyotrophic lateral sclerosis (ALS) mainly affects the motor neurons but may also include other organs such as the skin. We aimed to determine whether matrix metalloproteinases could provide a link between neuronal degeneration and skin alterations in ALS. We measured CSF, serum and skin tissue MMP-2 and MMP-9 using ELISA and malondialdehyde (MDA), a marker of lipid peroxidation, using High Performance Liquid Chromatography (HPLC) in 54 ALS patients and 36 controls. We found CSF and skin MMP-9 to be elevated in ALS as compared to controls (p<0.001, p=0.03, respectively). We observed CSF MMP-9 to be highest in patients with a rapid progressive course of disease (p=0.008). In contrast, we found no significant differences of CSF, serum or skin concentrations of MMP-2 as compared to controls. CSF MMP-2 concentrations decreased with duration of disease (p=0.04, R=-0.31). MDA was elevated in serum of ALS (p<0.001), though no correlation with MMP-2 or MMP-9 was observed. Our findings indicate a general upregulation of MMP-9 in ALS. MMP-9 seems to play a role in both neurodegeneration and skin changes in ALS and could thus be a common factor linking otherwise distant aspects of disease pathology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amyotrophic Lateral Sclerosis / blood
  • Amyotrophic Lateral Sclerosis / cerebrospinal fluid*
  • Amyotrophic Lateral Sclerosis / metabolism*
  • Chromatography, High Pressure Liquid
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Male
  • Malondialdehyde / blood
  • Malondialdehyde / cerebrospinal fluid
  • Malondialdehyde / metabolism
  • Matrix Metalloproteinase 2 / blood
  • Matrix Metalloproteinase 2 / cerebrospinal fluid
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / blood
  • Matrix Metalloproteinase 9 / cerebrospinal fluid
  • Matrix Metalloproteinase 9 / metabolism
  • Matrix Metalloproteinases / blood
  • Matrix Metalloproteinases / cerebrospinal fluid*
  • Matrix Metalloproteinases / metabolism*
  • Middle Aged
  • Skin / metabolism*
  • Time Factors


  • Malondialdehyde
  • Matrix Metalloproteinases
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9