Iron promotes oxidative cell death caused by bisretinoids of retina

Ueda, Keiko; Kim, Hye Jin; Zhao, Jin; Song, Ying; Dunaief, Joshua L.; Sparrow, Janet R.

doi:10.1073/pnas.1722601115

Cited by 58 publications

(72 citation statements)

References 71 publications

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“…Similarly, improved chelator platinum complexes and hydroxyurea derivatives could be designed for targeted delivery and better treatment in different types of cancer [10,11]. Investigations using deferiprone and other chelators are also in progress for targeting oxidative stress toxicity and malfunction in mitochondria, which have been implicated in cancer and other diseases [12,[31][32][33][34][35][36]. New therapeutic possibilities include the design of polymeric chelators for the extraction and removal of excess essential and xenobiotic metals in the gastrointestinal tract and in environmental pollution.…”

Section: Examples Of the Clinical Applications Of Chelator Metal Compmentioning

confidence: 99%

Advances on Chelation and Chelator Metal Complexes in Medicine

Kontoghiorghes¹

2020

IJMS

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Section: Examples Of the Clinical Applications Of Chelator Metal Compmentioning

confidence: 99%

Advances on Chelation and Chelator Metal Complexes in Medicine

Kontoghiorghes¹

2020

IJMS

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“…Recently, deferiprone (DFP), a potent iron chelator, has been shown to rescue RGCs and glaucomatous degeneration in a mouse model of glaucoma [ 127 , 128 ]. In Abca4 −/− mice, a widely used model of retinal degeneration, deferiprone reduced the oxidation-driven degradation of vital bisretinoids such as A2E [ 129 ]. In mice lacking ceruloplamin and hepaestin, which accumulate iron in the retina, salicylaldehyde isonicotinoyl hydrazine (SIH), a potent iron chelator, rescued the phenotype.…”

Section: Methodsmentioning

confidence: 99%

Retinal Degeneration and Alzheimer’s Disease: An Evolving Link

Ashok

Singh

Chaudhary

et al. 2020

IJMS

105

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Age-related macular degeneration (AMD) and glaucoma are degenerative conditions of the retina and a significant cause of irreversible blindness in developed countries. Alzheimer’s disease (AD), the most common dementia of the elderly, is often associated with AMD and glaucoma. The cardinal features of AD include extracellular accumulation of amyloid β (Aβ) and intracellular deposits of hyper-phosphorylated tau (p-tau). Neuroinflammation and brain iron dyshomeostasis accompany Aβ and p-tau deposits and, together, lead to progressive neuronal death and dementia. The accumulation of Aβ and iron in drusen, the hallmark of AMD, and Aβ and p-tau in retinal ganglion cells (RGC), the main retinal cell type implicated in glaucoma, and accompanying inflammation suggest overlapping pathology. Visual abnormalities are prominent in AD and are believed to develop before cognitive decline. Some are caused by degeneration of the visual cortex, while others are due to RGC loss or AMD-associated retinal degeneration. Here, we review recent information on Aβ, p-tau, chronic inflammation, and iron dyshomeostasis as common pathogenic mechanisms linking the three degenerative conditions, and iron chelation as a common therapeutic option for these disorders. Additionally discussed is the role of prion protein, infamous for prion disorders, in Aβ-mediated toxicity and, paradoxically, in neuroprotection.

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“…Only L1 has been shown to have antioxidant effects in the brain of Friedreich's ataxia and pantothenate kinase-associated neurodegeneration patients. 11,13,75,93,95,[161][162][163] patients with normal iron stores. 66,74 As a result of the DF limitations, no clear strategies have become available or promoted in the last 50 years for the complete elimination of excess iron and the normalisation of the iron stores in thalassaemia and other patients.…”

Section: Chelating Drug Antioxidant Effectsmentioning

confidence: 99%

“…74,75,[87][88][89][90][91] In particular, with regards to the latter, iron chelation therapy using L1 has been considered for the reduction of anticancer drug toxicity such as doxorubicin, for ophthalmic toxicity and neurotoxicity and also many other related applications. [92][93][94][95] The selection of therapeutic protocols for thalassaemia and other diseases involving chelating drugs is crucial because it affects risk/benefit assessment and therapeutic outcome, as well as morbidity and mortality of hundreds of thousands of patients. [96][97][98][99] The present state of generally 'random' selection of chelating drug protocols does not appear to benefit the patients.…”

Section: Chelating Drug Antioxidant Effectsmentioning

confidence: 99%

The History of Deferiprone (L1) and the Complete Treatment of Iron Overload in Thalassaemia

Kontoghiorghes¹,

Kleanthous²,

Kontoghiorghe³

2020

Mediterr J Hematol Infect Dis

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Deferiprone (L1) was originally designed, synthesised and screened in vitro and in vivo in 1981 by Kontoghiorghes G J following his discovery of the novel alpha-ketohydroxypyridine class of iron chelators (1978-1981), which were intended for clinical use. The journey through the years for the treatment of thalassaemia with L1 has been a very difficult one with intriguing turn of events, which continue until today. Despite many complications, such as the wide use of L1 suboptimal dose protocols, the aim of chelation therapy- namely the complete removal of excess iron in thalassaemia major patients, has been achieved following the introduction of specific L1 and L1/deferoxamine combinations. Many such patients continue to maintain normal iron stores. As a result of the introduction of L1, thalassaemia has changed from a fatal to a chronic disease and thalassaemia patients are active professional members in all sectors of society, have their own families with children and grandchildren and their lifespan is approaching that of normal individuals. No changes in the low toxicity profile of L1 have been observed in more than 30 years of clinical use. Thousands of thalassaemia patients are still denied the cardioprotective and other beneficial effects of L1 therapy. The safety of L1 in thalassaemia and other non-iron loaded diseases resulted in its selection as one of the leading therapeutics for the treatment of Friedreich’s ataxia, pantothenate kinase-associated neurodegeneration and other similar cases. There are also increasing prospects for the application of L1 as a main, alternative or adjuvant therapy in many pathological conditions including cancer, infectious diseases and as a general antioxidant for diseases related to free radical pathology.

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Iron promotes oxidative cell death caused by bisretinoids of retina

Cited by 58 publications

References 71 publications

Advances on Chelation and Chelator Metal Complexes in Medicine

Advances on Chelation and Chelator Metal Complexes in Medicine

Retinal Degeneration and Alzheimer’s Disease: An Evolving Link

The History of Deferiprone (L1) and the Complete Treatment of Iron Overload in Thalassaemia

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