Elamipretide

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Elamipretide

Description

Bendavia (Elamipretide) was developed as a mitochondria-targeted drug against degenerative diseases, including cardiac ischemia-reperfusion injury. Clinical trials showed variable results. It is a cationic tetrapeptide which readily passes cell membranes, associates with cardiolipin in the mitochondrial inner membrane. Supercomplex-associated CIV activity significantly improved in response to elamipretide treatment in the failing human heart.

Abbreviation: Bendavia

Reference: Chatfield 2019 JACC Basic Transl Sci

Elamipretide and mitObesity

Work in progress by Gnaiger E 2020-02-12 linked to a preprint in preparation on BME and mitObesity.

References: Bendavia (Elamipretide)

 YearReferenceOrganismTissue;cell
Chatfield 2019 JACC Basic Transl Sci2019Chatfield KC, Sparagna GC, Chau S, Phillips EK, Ambardekar AV, Aftab M, Mitchell MB, Sucharov CC, Miyamoto SD, Stauffer BL (2019) Elamipretide improves mitochondrial function in the failing human heart. JACC Basic Transl Sci 4:147-57.HumanHeart
Campbell 2018 Free Radic Biol Med2018Campbell MD, Duan J, Samuelson AT, Gaffrey MJ, Wang L, Bammler TK, Moore RJ, White CC, Kavanagh TJ, Voss JG, Szeto HH, Rabinovitch PS, Qian WJ, Marcinek DJ (2018) Improving mitochondrial function with SS-31 reverses age-related redox stress and improves exercise tolerance in aged mice. Free Radic Biol Med 134:268-81.MouseSkeletal muscle
Brown 2014 J Cardiovasc Pharmacol Ther2014Brown DA, Hale SL, Baines CP, del Rio CL, Hamlin RL, Yueyama Y, Kijtawornrat A, Yeh ST, Frasier CR, Stewart LM, Moukdar F, Shaikh SR, Fisher-Wellman KH, Neufer PD, Kloner RA (2014) Reduction of early reperfusion injury with the mitochondria-targeting peptide bendavia. J Cardiovasc Pharmacol Ther 19:121-32.RatHeart
 YearReferenceOrganismTissue;cell
Bamberger 2018 MiP20182018
MiPsociety
Discovery and development of elamipretide: targeting mitochondrial dysfunction in rare and common disease.
Marcinek 2016 Abstract MitoFit Science Camp 20162016Targeting mitochondrial redox stress reveals two phases for reversal of mitochondrial dysfunction in aged mouse skeletal muscle.MouseSkeletal muscle
Shaikh 2014 Circulation2014Shaikh SR, Moukdar F, Alleman RJ, Lark DS, Neufer PD, Brown D (2014) The cardiolipin-targeting peptide Bendavia improves post-ischemic mitochondrial energetics by sustaining native respiratory protein complexes. Am Heart Assoc 130:A17592.RatHeart
  1. https://www.ncbi.nlm.nih.gov/pubmed/29500292

MitoPedia: mitObesity drugs

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TermAbbreviationDescription
CurcuminCurcumin has been shown to possess significant anti-inflammatory, anti-oxidant, anti-carcinogenic, anti-mutagenic, anti-coagulant and anti-infective effects. The protective effects of curcumin on rat heart mitochondrial injuries induced by in vitro anoxia–reoxygenation were evaluated by Xu et al 2013. It was found that curcumin added before anoxia or immediately prior to reoxygenation exhibited remarkable protective effects against anoxia–reoxygenation induced oxidative damage to mitochondria.
ElamipretideBendaviaBendavia (Elamipretide) was developed as a mitochondria-targeted drug against degenerative diseases, including cardiac ischemia-reperfusion injury. Clinical trials showed variable results. It is a cationic tetrapeptide which readily passes cell membranes, associates with cardiolipin in the mitochondrial inner membrane. Supercomplex-associated CIV activity significantly improved in response to elamipretide treatment in the failing human heart.
FlavonoidsFlavonoids are a group of bioactive polyphenols with potential antioxidant and anti-inflammatory effects, abundant in fruits and vegetables, and in some medicinal herbs. Flavonoids are synthesized in plants from phenylalanine. Dietary intake of flavonoids as nutraceuticals is discussed for targeting T2D and other degenerative diseases.
MelatoninaMTMelatonin (N-acetyl-5-methoxytryptamine, aMT) is a highly conserved molecule present in unicellular to vertebrate organisms. Melatonin is synthesized from tryptophan in the pinealocytes by the pineal gland and also is produced in other organs, tissues and fluids (extrapineal melatonin). Melatonin has lipophilic and hydrophilic nature which allows it to cross biological membranes. Therefore, melatonin is present in all subcellular compartments predominantly in the nucleus and mitochondria. Melatonin has pleiotropic functions with powerful antioxidant, anti-inflammatory and oncostatic effects with a wide spectrum of action particularly at the level of mitochondria. » MiPNet article
MetforminMetformin is mainly known as an important antidiabetic drug which is effective, however, in a wide spectrum of degenerative diseases. It is an inhibitor of Complex I.
RapamycinRapamycin is an inhibitor of the mammalian/mechanistic target of rapamycin, complex 1 (mTORC1). Rapamycin induces autophagy and dyscouples mitochondrial respiration. Rapamycin delays senescence in human cells, and extends lifespan in mice without detrimental effects on mitochondrial fitness in skeletal muscle.
ResveratrolResveratrol is a natural bioactive phenol prouced by several plants with antioxidant and anti-inflammatory effects. Dietary intake as nutraceutical is discussed for targeting mitochondria with a wide spectrum of action in degenerative diseases.
SpermidineSpermidine is a polycationic bioactive polyamine mainly found in wheat germ, soybean and various vegetables, involved in the regulation of mitophagy, cell growth and cell death. Like other caloric restriction mimetics, spermidine is effective in cardioprotection, neuroprotection and anticancer immunosuppression by preserving mitochondrial function and control of autophagy.
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