Matrix metalloproteinases in the neocortex and spinal cord of amyotrophic lateral sclerosis patients

J Neurochem. 1996 Jul;67(1):251-9. doi: 10.1046/j.1471-4159.1996.67010251.x.


Matrix metalloproteinases (MMPs) were analyzed by immunohistochemistry and zymography in amyotrophic lateral sclerosis (ALS) and control brain and spinal cord specimens. Three major bands of enzyme activity (70, 100, and 130 kDa) were consistently observed and were subsequently identified as MMP-2 (70 kDa; also known as EC or gelatinase A) and MMP-9 (100 and 130 kDa; also known as EC or gelatinase B). Immunohistochemical studies established the presence of MMP-2 in astrocytes and MMP-9 in pyramidal neurons in the motor cortex and motor neurons in the spinal cord of ALS patients. Although a significant decrease in MMP-2 activity was noticed in the ALS motor cortex, statistically significant increases in MMP-9 (100-kDa) activity were observed in ALS frontal and occipital cortices (BA10 and 17) and all three spinal cord regions when compared with control specimens. The highest MMP-9 (100-kDa) activities in ALS were found in the motor cortex and thoracic and lumbar cord specimens. The abnormally high amount of MMP-9 and its possible release at the synapse may destroy the structural integrity of the surrounding matrix, thereby contributing to the pathogenesis of ALS.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amyotrophic Lateral Sclerosis / enzymology*
  • Blotting, Western
  • Cerebral Cortex / chemistry
  • Cerebral Cortex / cytology
  • Cerebral Cortex / enzymology*
  • Extracellular Matrix / chemistry
  • Extracellular Matrix / enzymology*
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Metalloendopeptidases / analysis*
  • Metalloendopeptidases / metabolism
  • Middle Aged
  • Motor Neurons / chemistry
  • Motor Neurons / enzymology
  • Serine Proteinase Inhibitors / analysis
  • Serine Proteinase Inhibitors / metabolism
  • Spinal Cord / chemistry
  • Spinal Cord / cytology
  • Spinal Cord / enzymology*
  • alpha 1-Antichymotrypsin / analysis
  • alpha 1-Antichymotrypsin / metabolism


  • Serine Proteinase Inhibitors
  • alpha 1-Antichymotrypsin
  • Metalloendopeptidases