title: Linking neuron and skin: matrix metalloproteinases in amyotrophic lateral sclerosis (ALS).
abstract: 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.
authors.affiliation: Department of Neurology, University of Ulm, Oberer Eselsberg 45, 89081 Ulm, Germany.
authors.forename: Lubin
authors.initials: L
authors.lastname: Fang
authors.forename: Friederike
authors.initials: F
authors.lastname: Huber-Abel
authors.forename: Marko
authors.initials: M
authors.lastname: Teuchert
authors.forename: Corinna
authors.initials: C
authors.lastname: Hendrich
authors.forename: Johannes
authors.initials: J
authors.lastname: Dorst
authors.forename: Dagmar
authors.initials: D
authors.lastname: Schattauer
authors.forename: Heinz
authors.initials: H
authors.lastname: Zettlmeissel
authors.forename: Meinhard
authors.initials: M
authors.lastname: Wlaschek
authors.forename: Karin
authors.initials: K
authors.lastname: Scharffetter-Kochanek
authors.forename: Hayrettin
authors.initials: H
authors.lastname: Tumani
authors.forename: Albert C
authors.initials: AC
authors.lastname: Ludolph
authors.forename: Johannes
authors.initials: J
authors.lastname: Brettschneider
mesh_terms: 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
chemical_list: D008315:Malondialdehyde; D020782:Matrix Metalloproteinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9