Cell-permeable peptide antioxidants as a novel therapeutic approach in a mouse model of amyotrophic lateral sclerosis

Petri, Susanne; Kiaei, Mahmoud; Damiano, Maria; Hiller, Andrew; Wille, Elizabeth; Manfredi, Giovanni; Calingasan, Noel Y.; Szeto, Hazel H.; Beal, M. Flint

doi:10.1055/s-2006-952989

Cited by 25 publications

(36 citation statements)

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“…In ischemia-reperfusion, SS31 reduced CD36 expression, and ligand levels by inhibiting LDL peroxidation [95]. These small peptides are neuroprotective against MPTP [96] and in a transgenic mouse model of ALS [97]. SS-31 also protected against amyloid toxicity in vitro and in vivo by increasing neurite outgrowth, rescuing mitochondrial structure and function and decreasing cyclophilin D expression [98].…”

Section: Neuroprotective Strategies Targeting Mitochondriamentioning

confidence: 99%

Neuroprotective strategies involving ROS in Alzheimer disease

Dumont

Beal

2011

Free Radical Biology and Medicine

355

247

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Alzheimer's disease (AD) is a neurodegenerative disorder in which oxidative stress is a key hallmark. It occurs early in disease pathogenesis and can exacerbate its progression. Several causes of oxidative stress have been determined over the years. First, mitochondria play an important role in the generation and accumulation of free radicals. In addition to mitochondria, inflammation can also induce oxidative damage, especially via microglia, and microglia are also important for Aβ clearance. In AD, both mitochondrial function and inflammatory response are affected, leading to increased ROS formation and oxidative damage to lipid, proteins and nucleic acids. Some other sources have also been identified.From these findings, various neuroprotective strategies against ROS-mediated damages have been elaborated in AD research. This review recapitulates some of the major strategies used to prevent oxidative stress and disease progression. Outcomes from in vitro and in vivo studies using models of AD are encouraging. However, only a few clinical trials have provided positive results in terms of slowing down cognitive decline.Nonetheless, there is still hope for improved compounds that would better target pathways implicated in ROS production. In fact, facilitating the endogenous antioxidant system by modulating transcription has great promise for AD therapy.

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Section: Neuroprotective Strategies Targeting Mitochondriamentioning

confidence: 99%

Neuroprotective strategies involving ROS in Alzheimer disease

Dumont

Beal

2011

Free Radical Biology and Medicine

355

247

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“…To date, the use of mitochondria-targeted drugs, such as MitoQ (a CoQ10 derivative conjugated to TPP) or SS-31 peptides have been successful in animal models of neurodegenerative diseases such as PD (Ghosh et al, 2010) and ALS (Petri et al, 2006), thus paving the way to use this strategy in mitochondrial diseases. Mitochondria targeting allows a high concentration of the compounds to reach the organelle, increasing their potency and minimizing extra-mitochondrial metabolism.…”

Section: Targeting Mitochondriamentioning

confidence: 99%

Mitochondrial dysfunction in central nervous system white matter disorders

Morató

Bertini

Verrigni

et al. 2014

Glia

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Defects of mitochondrial respiration and function had been proposed as a major culprit in the most common neurodegenerative diseases, including prototypic diseases of central nervous system (CNS) white matter such as multiple sclerosis. The importance of mitochondria for white matter is best exemplified in a group of defects of the mitochondria oxidative metabolism called mitochondria leukoencephalopathies or encephalomyopathies. These diseases are clinically and genetically heterogeneous, given the dual control of the respiratory chain by nuclear and mitochondrial DNA, which makes the precise diagnosis and classification challenging. Our understanding of disease pathogenesis is nowadays still limited. Here, we review current knowledge on pathogenesis and genetics, outlining diagnostic clues for the various forms of mitochondria disease. In particular, we underscore the value of magnetic resonance imaging (MRI) for the differential diagnosis of specific types of mitochondrial leukoencephalopathies, such as genetic defects on SDHFA1. The use of novel technologies for gene identification, such as whole-exome sequencing studies, is expected to shed light on novel molecular etiologies, broadening prenatal diagnosis, disease understanding, and therapeutic options. Current treatments are mostly palliative, but very promising novel gene and pharmacologic therapies are emerging, which may also benefit a growing list of secondary mitochondriopathies, such as the peroxisomal disease adrenoleukodystrophy.

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“…It decreases mitochondrial ROS production and inhibits PTP and mitochondrial depolarization in isolated mitochondria [119]. Daily injections of SS-31 into G93A SOD1 mutants, an animal model of ALS, before onset of symptoms, lead to a significant increase in survival and improvement of motor performance [121]. Recently, Yang and collaborators [122] examined the ability of SS-31 and SS-20, to protect against MPTP neurotoxicity in mice.…”

Section: Mitochondrial-directed Therapiesmentioning

confidence: 99%

Mitochondria: A therapeutic target in neurodegeneration

Moreira¹,

Zhu²,

Wang³

et al. 2010

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

255

172

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SUMMARY Mitochondrial dysfunction has long been associated with neurodegenerative disease. Therefore, mitochondrial protective agents represent a unique direction for the development of drug candidates that can modify the pathogenesis of neurodegeneration. This review discusses evidence showing that mitochondrial dysfunction has a central role in the pathogenesis of Alzheimer’s, Parkinson’s and Huntington’s diseases and amyotrophic lateral sclerosis. We also debate the potential therapeutic efficacy of metabolic antioxidants, mitochondria-directed antioxidants and Szeto-Schiller (SS) peptides. Since these compounds preferentially target mitochondria, a major source of oxidative damage, they are promising therapeutic candidates for neurodegenerative diseases. Furthermore, we will briefly discuss the novel action of the antihistamine drug Dimebon on mitochondria.

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Cell-permeable peptide antioxidants as a novel therapeutic approach in a mouse model of amyotrophic lateral sclerosis

Cited by 25 publications

References 0 publications

Neuroprotective strategies involving ROS in Alzheimer disease

Neuroprotective strategies involving ROS in Alzheimer disease

Mitochondrial dysfunction in central nervous system white matter disorders

Mitochondria: A therapeutic target in neurodegeneration

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