Sirtuins as therapeutic targets of ALS

Pasinetti, Giulio Maria; Bilski, Amanda; Zhao, Wei

doi:10.1038/cr.2013.94

Cited by 19 publications

(17 citation statements)

References 10 publications

(12 reference statements)

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“…Interestingly, co‐expression with either SIRT3 or PGC‐1α is able to rescue SOD1 G93A ‐induced mitochondrial fragmentation to improve cell survival (Song et al ., ). SIRT3 regulates ketone body production by deacetylation of mitochondrial 3‐hydroxy‐3‐methylglutaryl CoA synthase 2 (HMGCS2), indicating its potential for neuroprotection in the SOD1 G93A model (Pasinetti et al ., ).…”

Section: The Role Of Sirt3 In Other Diseasesmentioning

confidence: 97%

Function of the SIRT3 mitochondrial deacetylase in cellular physiology, cancer, and neurodegenerative disease

et al. 2016

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SummaryIn mammals, seven members of the sirtuin protein family known as class III histone deacetylase have been identified for their characteristic features. These distinguished characteristics include the tissues where they are distributed or located, enzymatic activities, molecular functions, and involvement in diseases. Among the sirtuin members, SIRT3 has received much attention for its role in cancer genetics, aging, neurodegenerative disease, and stress resistance. SIRT3 controls energy demand during stress conditions such as fasting and exercise as well as metabolism through the deacetylation and acetylation of mitochondrial enzymes. SIRT3 is well known for its ability to eliminate reactive oxygen species and to prevent the development of cancerous cells or apoptosis. This review article provides a comprehensive review on numerous (noteworthy) molecular functions of SIRT3 and its effect on cancer cells and various diseases including Huntington's disease, amyotrophic lateral sclerosis, and Alzheimer's disease.

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Section: The Role Of Sirt3 In Other Diseasesmentioning

confidence: 97%

Function of the SIRT3 mitochondrial deacetylase in cellular physiology, cancer, and neurodegenerative disease

et al. 2016

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“…Furthermore, resveratrol, a polyphenol that exhibits beneficial effects in NDs, protects against WD by activating Sirtuin 1 through dissociation from its inhibitor DBC1 (Calliari et al, 2014 ). There is evidence indicating that the metabolites obtained from NADH play a crucial role on the effect of Sirtuins (Jasper, 2013 ), and considering that these metabolites, especially nicotinamide mononucleotide (NMN), are crucial in the axonal degenerative process (Di Stefano et al, 2017 ), it seems plausible that sirtuins and NAD + metabolism might play a central role on the ALS pathomechanism, even as a potential therapeutic target for the disease (Pasinetti et al, 2013 ; Tang, 2016 ).…”

Section: Axonal Degeneration At Early Stages Of Age-related Neurodegementioning

confidence: 99%

Axonal Degeneration during Aging and Its Functional Role in Neurodegenerative Disorders

et al. 2017

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Aging constitutes the main risk factor for the development of neurodegenerative diseases. This represents a major health issue worldwide that is only expected to escalate due to the ever-increasing life expectancy of the population. Interestingly, axonal degeneration, which occurs at early stages of neurodegenerative disorders (ND) such as Alzheimer's disease, Amyotrophic lateral sclerosis, and Parkinson's disease, also takes place as a consequence of normal aging. Moreover, the alteration of several cellular processes such as proteostasis, response to cellular stress and mitochondrial homeostasis, which have been described to occur in the aging brain, can also contribute to axonal pathology. Compelling evidence indicate that the degeneration of axons precedes clinical symptoms in NDs and occurs before cell body loss, constituting an early event in the pathological process and providing a potential therapeutic target to treat neurodegeneration before neuronal cell death. Although, normal aging and the development of neurodegeneration are two processes that are closely linked, the molecular basis of the switch that triggers the transition from healthy aging to neurodegeneration remains unrevealed. In this review we discuss the potential role of axonal degeneration in this transition and provide a detailed overview of the literature and current advances in the molecular understanding of the cellular changes that occur during aging that promote axonal degeneration and then discuss this in the context of ND.

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“…Other compounds that directly or indirectly affect energy metabolism such as sirtuins prevent fragmentation of mitochondria and promote an increase in ketone levels and are potential therapeutic targets in ALS (Körner et al, 2013a; Pasinetti et al, 2013). Resveratrol, an antioxidant, which is believed to increase sirtuin 1 expression, was able to delay onset of symptoms, prevent motor neuron loss and extend survival when treatment was initiated at early stages of the disease in hSOD1 G93A mice (Mancuso et al, 2014; Song et al, 2014).…”

Section: Metabolic Treatments In Alsmentioning

confidence: 99%

Metabolic Dysfunctions in Amyotrophic Lateral Sclerosis Pathogenesis and Potential Metabolic Treatments

Tefera

Borges

2017

Front. Neurosci.

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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease primarily characterized by loss of motor neurons in brain and spinal cord. The death of motor neurons leads to denervation of muscle which in turn causes muscle weakness and paralysis, decreased respiratory function and eventually death. Growing evidence indicates disturbances in energy metabolism in patients with ALS and animal models of ALS, which are likely to contribute to disease progression. Particularly, defects in glucose metabolism and mitochondrial dysfunction limit the availability of ATP to CNS tissues and muscle. Several metabolic approaches improving mitochondrial function have been investigated in vitro and in vivo and showed varying effects in ALS. The effects of metabolic approaches in ALS models encompass delays in onset of motor symptoms, protection of motor neurons and extension of survival, which signifies an important role of metabolism in the pathogenesis of the disease. There is now an urgent need to test metabolic approaches in controlled clinical trials. In addition, more detailed studies to better characterize the abnormalities in energy metabolism in patients with ALS and ALS models are necessary to develop metabolically targeted effective therapies that can slow the progression of the disease and prolong life for patients with ALS.

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Sirtuins as therapeutic targets of ALS

Cited by 19 publications

References 10 publications

Function of the SIRT3 mitochondrial deacetylase in cellular physiology, cancer, and neurodegenerative disease

Function of the SIRT3 mitochondrial deacetylase in cellular physiology, cancer, and neurodegenerative disease

Axonal Degeneration during Aging and Its Functional Role in Neurodegenerative Disorders

Metabolic Dysfunctions in Amyotrophic Lateral Sclerosis Pathogenesis and Potential Metabolic Treatments

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