Linking neuron and skin: matrix metalloproteinases in amyotrophic lateral sclerosis (ALS).
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.
Fang
Lubin
L
Department of Neurology, University of Ulm, Oberer Eselsberg 45, 89081 Ulm, Germany.
Huber-Abel
Friederike
F
Teuchert
Marko
M
Hendrich
Corinna
C
Dorst
Johannes
J
Schattauer
Dagmar
D
Zettlmeissel
Heinz
H
Wlaschek
Meinhard
M
Scharffetter-Kochanek
Karin
K
Tumani
Hayrettin
H
Ludolph
Albert C
AC
Brettschneider
Johannes
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood / Q000134:cerebrospinal fluid* / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008315:Malondialdehyde / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000097:blood / Q000134:cerebrospinal fluid* / Q000378:metabolism*; D008875:Middle Aged; D012867:Skin / Q000378:metabolism*; D013997:Time Factors
D008315:Malondialdehyde; D020782:Matrix Metalloproteinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9