1999
DOI: 10.1038/6568
|View full text |Cite
|
Sign up to set email alerts
|

Neuroprotective effects of creatine in a transgenic animal model of amyotrophic lateral sclerosis

Abstract: Mitochondria are particularly vulnerable to oxidative stress, and mitochondrial swelling and vacuolization are among the earliest pathologic features found in two strains of transgenic amyotrophic lateral sclerosis (ALS) mice with SOD1 mutations. Mice with the G93A human SOD1 mutation have altered electron transport enzymes, and expression of the mutant enzyme in vitro results in a loss of mitochondrial membrane potential and elevated cytosolic calcium concentration. Mitochondrial dysfunction may lead to ATP d… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
2
1

Citation Types

11
364
0
6

Year Published

2000
2000
2015
2015

Publication Types

Select...
7
2

Relationship

0
9

Authors

Journals

citations
Cited by 644 publications
(381 citation statements)
references
References 22 publications
11
364
0
6
Order By: Relevance
“…Creatine stabilizes mitochondrial CK and inhibits opening of the mitochondrial transition pore (O'Gorman et al, 1996). Creatine administration to G93A transgenic mice protected them from increases in biochemical indices of oxidative damage (Klivenyi et al, 1999).…”
Section: Discussionmentioning
confidence: 99%
“…Creatine stabilizes mitochondrial CK and inhibits opening of the mitochondrial transition pore (O'Gorman et al, 1996). Creatine administration to G93A transgenic mice protected them from increases in biochemical indices of oxidative damage (Klivenyi et al, 1999).…”
Section: Discussionmentioning
confidence: 99%
“…Several reports have shown positive e ects of creatine and its analogs on neuronal survival in culture following stress with glutamate or betaamyloid, 18 as well as in vivo in the brains of newborn mammals under conditions of anoxia. 20,25,36 In transgenic mice models of ALS 22 and Huntington's disease 23 creatine was shown to increase life span and improve motor behavior. Indeed, the recent study by Sullivan and coworkers shows that creatine brings about a signi®cant neuroprotection in traumatic brain injury by decreasing the extent of cortical damage by as much as 50% in rats.…”
Section: Discussionmentioning
confidence: 99%
“…17 Supplementation of muscle cells or neurons with the high-energy phosphate precursor creatine is known to improve cellular energy levels, eg PCr/ATP ratio, and to exert a protective e ect against a variety of stressors. 18 ± 21 In animal models of several neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) 22 and Huntington's disease, 23 creatine has proven to be a remarkably potent neuroprotective agent. Orally supplemented creatine is transported by a speci®c creatine transporter into muscle and neural tissues 24 as measured non-invasively by 31 P-NMP spectroscopy, giving rise to a signi®cantly increased PCr/ATP ratio in the rat brain 25 or by 1H-NMR spectroscopy in either creatine-de®cient patients 26 or healthy subjects, 27 showing that total creatine concentration is elevated in the brain after creatine supplementation.…”
Section: Introductionmentioning
confidence: 99%
“…These mice replicate much of the human ALS phenotype. They develop eventual paralysis of their hindlimbs at approximately 120 days of age subsequent to mitochondrial damage, an accumulation of extracellular glutamate and intracellular filamentous inclusions, motor neuron (MN) cell death, and loss of axons innervating the muscle [(Gurney et al 1994;Klivenyi et al 1999;Alexander et al 2000;Fischer et al 2004)]. …”
Section: Introductionmentioning
confidence: 99%