Resveratrol upregulated heat shock proteins and extended the survival of G93A-SOD1 mice

Han, Sung Hee; Choi, Jong-Ryoul; Shin, Ki Soon; Kang, Seok-Jίn

doi:10.1016/j.brainres.2012.09.022

Cited by 75 publications

(64 citation statements)

References 22 publications

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“…There is some controversy about the in vivo effect of resveratrol administration in SOD1 G93A mice. Markert et al [53] reported that dietary resveratrol given at 25 mg/kg did not produce functional effects, whereas Han et al [54] showed that intraperitoneal administration of resveratrol at 20 mg/kg led to improved functional outcome although less important than found in our study. A likely explanation of such discrepancies would be the differences in the dose and the route of administration.…”

Section: Discussioncontrasting

confidence: 74%

Resveratrol Improves Motoneuron Function and Extends Survival in SOD1G93A ALS Mice

et al. 2014

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Amyotrophic lateral sclerosis (ALS) is an adult onset neurodegenerative disease that causes progressive paralysis and death due to degeneration of motoneurons in spinal cord, brainstem and motor cortex. Nowadays, there is no effective therapy and patients die 2-5 years after diagnosis. Resveratrol (trans-3,4′,5-trihydroxystilbene) is a natural polyphenol found in grapes, with promising neuroprotective effects since it induces expression and activation of several neuroprotective pathways involving Sirtuin1 and AMPK. The objective of this work was to assess the effect of resveratrol administration on SOD1 G93A ALS mice. We determined the onset of symptoms by rotarod test and evaluated upper and lower motoneuron function using electrophysiological tests.We assessed the survival of the animals and determined the number of spinal motoneurons. Finally, we further investigated resveratrol mechanism of action by means of western blot and immunohistochemical analysis. Resveratrol treatment from 8 weeks of age significantly delayed disease onset and preserved lower and upper motoneuron function in female and male animals. Moreover, resveratrol significantly extended SOD1 G93A mice lifespan and promoted survival of spinal motoneurons. Delayed resveratrol administration from 12 weeks of age also improved spinal motoneuron function preservation and survival. Further experiments revealed that resveratrol protective effects were associated with increased expression and activation of Sirtuin 1 and AMPK in the ventral spinal cord. Both mediators promoted normalization of the autophagic flux and, more importantly, increased mitochondrial biogenesis in the SOD1 G93A spinal cord. Taken together, our findings suggest that resveratrol may represent a promising therapy for ALS.

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Section: Discussioncontrasting

confidence: 74%

Resveratrol Improves Motoneuron Function and Extends Survival in SOD1G93A ALS Mice

et al. 2014

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“…Studies using resveratrol, a polyphenolic compound that activates SIRT1 and other targets, have shown mixed effects in the SOD1 G93A mouse model of ALS, with some dosing regimens showing protection and others indicating no effect on disease progression (Han, Choi, Soon Shin, & Kang, 2012; Kim et al, 2007; Mancuso et al, 2014; Markert, Kim, Gifondorwa, Childers, & Milligan, 2010; Song, Chen, & Zhang, 2014). Overexpressing PGC1α slows ALS‐related pathologies in SOD1 G93A mice (Zhao et al, 2011), and more directly, elevating SIRT1 expression using the prion promoter has shown lifespan extension in the SOD1 G93A low copy transgenic mouse line (Watanabe et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

SIRT1 deacetylase in aging‐induced neuromuscular degeneration and amyotrophic lateral sclerosis

et al. 2018

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SIRT1 is an NAD+‐dependent deacetylase that functions in a variety of cells and tissues to mitigate age‐associated diseases. However, it remains unknown if SIRT1 also acts to prevent pathological changes that accrue in motor neurons during aging and amyotrophic lateral sclerosis (ALS). In this study, we show that SIRT1 expression decreases in the spinal cord of wild‐type mice during normal aging. Using mouse models either overexpressing or lacking SIRT1 in motor neurons, we found that SIRT1 slows age‐related degeneration of motor neurons’ presynaptic sites at neuromuscular junctions (NMJs). Transcriptional analysis of spinal cord shows an overlap of greater than 90% when comparing alterations during normal aging with changes during ALS, revealing a substantial upregulation in immune and inflammatory response genes and a downregulation of synaptic transcripts. In addition, overexpressing SIRT1 in motor neurons delays progression to end‐stage disease in high copy SOD1G93A mice. Thus, our findings suggest that there are parallels between ALS and aging, and interventions to impede aging may also slow the progression of this devastating disease.

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“…Our recent findings suggest that medium chain triglyceride (MCT) treatment could lead to an increased blood ketone level, protect motor neuron loss and attenuate ALS-type motor impairment, possibly through promoting oxygen consumption rate [6]. Altered sirtuin levels have been observed in both SOD1-G93A mouse models [7] and patient tissue [8], suggesting that the sirtuin family may be a disease target both in ALS mouse models and humans. Although treatment with dietary resveratrol, a SIRT1 activator, was not sufficient to exert any impact on disease outcomes, intraperitoneal injection of resveratrol led to a significant improvement in both symptoms and survival in the SOD1-G93A mouse model of ALS [7].…”

mentioning

confidence: 99%

“…Altered sirtuin levels have been observed in both SOD1-G93A mouse models [7] and patient tissue [8], suggesting that the sirtuin family may be a disease target both in ALS mouse models and humans. Although treatment with dietary resveratrol, a SIRT1 activator, was not sufficient to exert any impact on disease outcomes, intraperitoneal injection of resveratrol led to a significant improvement in both symptoms and survival in the SOD1-G93A mouse model of ALS [7]. These different findings may be due to the short half-life of resveratrol as well as different routes of administration.…”

mentioning

confidence: 99%

Sirtuins as therapeutic targets of ALS

2013

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Resveratrol upregulated heat shock proteins and extended the survival of G93A-SOD1 mice

Cited by 75 publications

References 22 publications

Resveratrol Improves Motoneuron Function and Extends Survival in SOD1G93A ALS Mice

Resveratrol Improves Motoneuron Function and Extends Survival in SOD1G93A ALS Mice

SIRT1 deacetylase in aging‐induced neuromuscular degeneration and amyotrophic lateral sclerosis

Sirtuins as therapeutic targets of ALS

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