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          Institute: MPI für experimentelle Medizin     Collection: Clinical Neuroscience     Display Documents



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ID: 292143.0, MPI für experimentelle Medizin / Clinical Neuroscience
Reduced oxidative damage in ALS by high-dose enteral melatonin treatment
Authors:Weishaupt, Jochen H.; Bartels, Claudia; Pölking, Esther; Dietrich, Jeannine; Rohde, Gundula; Poeggeler, Burkhard; Mertens, Nina; Sperling, Swetlana; Bohn, Matthias; Hüther, Gerald; Schneider, Armin; Bach, Alfred; Sirén, Anna-Leena; Hardeland, Rüdiger; Bähr, Mathias; Nave, Klaus-Armin; Ehrenreich, Hannelore
Language:English
Date of Publication (YYYY-MM-DD):2006-11
Title of Journal:Journal of Pineal Research
Journal Abbrev.:J Pineal Res
Volume:41
Issue / Number:4
Start Page:313
End Page:323
Review Status:Peer-review
Audience:Experts Only
Abstract / Description:Amyotrophic lateral sclerosis (ALS) is the collective term for a fatal motoneuron disease of different etiologies, with oxidative stress as a common molecular denominator of disease progression. Melatonin is an amphiphilic molecule with a unique spectrum of antioxidative effects not conveyed by classical antioxidants. In preparation of a possible future clinical trial, we explored the potential of melatonin as neuroprotective compound and antioxidant in: (1) cultured motoneuronal cells (NSC-34), (2) a genetic mouse model of ALS (SOD1(G93A)-transgenic mice), and (3) a group of 31 patients with sporadic ALS. We found that melatonin attenuates glutamate-induced cell death of cultured motoneurons. In SOD1(G93A)-transgenic mice, high-dose oral melatonin delayed disease progression and extended survival. In a clinical safety study, chronic high-dose (300 mg/day) rectal melatonin was well tolerated during an observation period of up to 2 yr. Importantly, circulating serum protein carbonyls, which provide a surrogate marker for oxidative stress, were elevated in ALS patients, but were normalized to control values by melatonin treatment. This combination of preclinical effectiveness and proven safety in humans suggests that high-dose melatonin is suitable for clinical trials aimed at neuroprotection through antioxidation in ALS.
Free Keywords:amyotrophic lateral sclerosis; human safety study; melatonin; motoneurons; neuroprotection; reactive oxygen species; transgenic models AMYOTROPHIC-LATERAL-SCLEROSIS; GLUTAMATE TRANSPORTER EAAT2; MOTOR-NEURON DEGENERATION; TRANSGENIC MOUSE MODEL; SUPEROXIDE-DISMUTASE; VITAMIN-E; PROLONGS SURVIVAL; MODIFIED PROTEINS; NERVOUS-SYSTEM; CLINICAL-TRIAL
External Publication Status:published
Document Type:Article
Communicated by:Hannelore Ehrenreich
Affiliations:MPI für experimentelle Medizin/Clinical neuroscience
MPI für experimentelle Medizin/Neurogenetics
Identifiers:ISSN:0742-3098 [ID No:1]
ISI:000240921200003 [ID No:2]
ISI:000240921200003 [ID No:3]
DOI:10.1111/j.1600-079X.2006.00377.x
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