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Reduced oxidative damage in ALS by high‐dose enteral melatonin treatment
Author(s) -
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 AnnaLeena,
Hardeland Rüdiger,
Bähr Mathias,
Nave KlausArmin,
Ehrenreich Hannelore
Publication year - 2006
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2006.00377.x
Subject(s) - melatonin , neuroprotection , oxidative stress , medicine , sod1 , amyotrophic lateral sclerosis , free radical scavenger , pharmacology , endocrinology , disease , superoxide dismutase
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.