Matrix Metalloproteinases in the Neocortex and Spinal Cord of Amyotrophic Lateral Sclerosis Patients

Abstract

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 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 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 (BA1O 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. Key Words: Matrix metalloproteinase-CNS-Amyotrophic lateral sclerosisa 1 -Antichymotrypsin -Astrocyte-Motor neuron.

Matrix metalloproteinases and their inhibitors in human traumatic spinal cord injury

“…A number of reports have indicated that MMPs are involved in the pathogenesis of a wide range of diseases and disorders of the CNS, including neurodegenerative diseases such as Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease and progressive supranuclear cerebral palsy [10][11][12][13][14] as well as stroke injuries [15]. It has been suggested that this class of extracellular proteases may be appropriate molecular targets to reduce secondary tissue degeneration and improve functional outcome [7,16].…”

Matrix Metalloproteinase-9 Undergoes Expression and Activation during Dendritic Remodeling in Adult Hippocampus

“…Considering that past results have been inconsistent with respect to the cellular localization of MMPs in the brain (Del-Bigio and Jacque, 1995;Backstrom et al, 1996;Gottschall and Deb, 1996;Lim et al, 1996;Romanic et al, 1998), we first investigated the tissue distribution of MMPs within the rat forebrain by means of in situ hybridization and immunocytochemistry. Coronal sections of 2-month old rat brains were analyzed at the level of the dorsal hippocampus (Fig.…”

Matrix metalloproteinases and their endogenous inhibitors in neuronal physiology of the adult brain

“…This notion appears surprising in the context of the previously described data implicating MMP-9 in neuronal plasticity. However, although under the variety of neurodegenerative conditions (ischemia, brain trauma, viral infections, amyotrophic lateral sclerosis, ALS, Parkinson's disease, PD, Alzheimer's disease, AD) MMP-9 still remains mainly neuronal in origin, it is not clear whether it is expressed by the neurons prone to death and/or those attempting to recover from the damage [12,20,31,32,43,[57][58][59]. As it has recently been pointed out that both possibilities should be equally considered [60].…”