MATRIX METALLOPROTEINASES IN THE NEOCORTEX AND SPINAL-CORD OF AMYOTROPHIC-LATERAL-SCLEROSIS PATIENTS

Matrix metalloproteinases (MMPs) were analyzed by immunohistochemistry and zymography in amyotrophic lateral sclerosis (ALS) and control bra in and spinal cord specimens, Three major bands of enzyme activity (70 , 100, and 130 kDa) were consistently observed and were subsequently i dentified as MMP-2 (70 kDa; also known as EC 3.4.24.24 or gelatinase A ) and MMP-9 (100 and 130 kDa; also known as EC 3.4.24.35 or gelatinase B), Immunohistochemical studies established the presence of MM P-2 in astrocytes and MMP-9 in pyramidal neurons in the motor cortex and mot or neurons in the spinal cord of ALS patients. Although a significant decrease in MMP-2 activity was noticed in the ALS motor cortex, statis tically significant increases in MMP-9 (100-kDa) activity were observe d in ALS frontal and occipital cortices (BA10 and 17) and all three sp inal cord regions when compared with control specimens. The highest MM P-9 (100-kDa) activities in ALS were found in the motor cortex and tho racic and lumbar cord specimens. The abnormally high amount of MMP-9 a nd its possible release at the synapse may destroy the structural inte grity of the surrounding matrix, thereby contributing to the pathogene sis of ALS.