Glutathione, Cysteine, and the Neuromelanin Pathway : Potential Roles in the Pathogenesis of Parkinson’s Disease—a New Hypothesis
Christopher A. Shaw in Glutathione in the Nervous System, 2018
However, it has recently been reported that a rare, genetic form of PD results from a mutation of the ceruloplasmin gene located on chromosome 3 (Harris et al. 1995). Patients with aceruloplasminemia have very low levels of ceruloplasmin, a protein that appears to be involved in iron transport out of cells. Thus, it is probably the high levels of iron present in the basal ganglia of these patients that mediates HO• formation and oxidative damage to dopamineigic neurons. It is also of relevance to note that the decreased levels of GSH measured in the SN in PD also occur in incidental Lewy-body disease (Dexter et al. 1993).
Degenerative Diseases of the Nervous System
Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw in Hankey's Clinical Neurology, 2020
NBIA:50 a heterogeneous group of genetic disorders characterized by brain iron accumulation and neuronal death. Subtypes may be recognized by pattern of iron deposition on T2* and fast spin echo MRI sequences: PKAN: Rare, sometimes familial, condition of progressive rigidity, bradykinesia, dystonia, dysarthria, and dementia in childhood, or occasionally adulthood.Epileptic seizures, chorea, cerebellar ataxia, muscle atrophy, and retinitis pigmentosa may also occur.Iron-containing pigment deposited in the substantia nigra and globus pallidus (‘eye of the tiger sign’) can be imaged by MRI (Figure 16.66).Neuroferritinopathy: more prominent chorea and dystonia; MRI demonstrates more involvement of dentate nuclei, globus pallidus, and putamen, along with confluent areas of hyperintensity.Aceruloplasminemia: occurs with ataxia, dystonia, and chorea, as well as retinal degeneration and diabetes mellitus; MRI demonstrates low intensity in the striatum, thalamus, and dentate nucleus.Infantile neuroaxonal dystrophy.
Potential of Application of Iron Chelating Agents in Ophthalmic Diseases
Published in Seminars in Ophthalmology, 2021
Alireza Ghaffarieh, Joseph B. Ciolino
Age-related macular degeneration is a common cause of irreversible vision loss worldwide.42 The Age-Related Eye Disease Study (AREDS) reported in 2001 that antioxidant vitamins plus zinc were effective in reducing the risk of AMD progression.43 Iron is likely to be an important cause of oxidative stress in AMD.44 Elevated iron levels have also been found in the photoreceptor layer of the postmortem macula of a patient with GA.44 When iron levels in aqueous humor were measured in patients with cataract surgery, they were increased by more than two-fold in patients with non-exudative AMD.45 Although iron accumulation was discovered in AMD retinas, its role in the pathogenesis remains unproven, but some evidence suggests a causal link. Retinal iron levels increase with age.46 Aceruloplasminemia had drusen-like deposits in the retina at an uncharacteristically young age.47 Double knockout mice with iron accumulation in the neural retina and RPE have retinal degeneration sharing features of AMD.48 The extracellular iron-binding protein transferrin is up regulated in AMD retinas.49
Serum ceruloplasmin monitoring in a case of silver intoxication due to intravenous silver infusion
Published in Clinical Toxicology, 2022
Chun-yiu Law, Siu-chung Leung, Florence Loong, Tsz-ki Ling, Ka-chung Wong, Nike Kwai-cheung Lau, Sik-hon Tsui, Ching-lung Lai, Ching-wan Lam
The pathomechanism of silver-induced damage is believed to be reactive oxygen species (ROS)-related [12]. The lack of ferrous oxidase activity in Ag-Cp could partly explain the ROS stress in multiple organs, for example, liver and brain. This oxidase is physiologically vital which oxidize intracellular ferrous (Fe2+) to ferric (Fe3+) ions and allows subsequent Fe3+ exocytosis with incorporation to circulating transferrin. Indeed, a low circulating iron and transferrin and high ferritin was presented in our case. The pattern is similar to hereditary aceruloplasminemia; our patient, likewise also complained of cognitive decline [13]. Nevertheless, ferritin is a positive acute phase reactant and hyperferritinemia could also be secondary to an inflammatory process. Yet, non-transferrin-bound Fe2+ could cause oxidative stress with damages via Fenton reaction. The liver biochemistry and histology are suggestive of chronic liver disease in this patient. Since this patient is neither an alcoholic nor a viral hepatitis carrier, and his liver function improved after silver cessation, it is likely that silver has contributed to his liver derangement. However, we cannot ascertain the causal effect here since we do not have his baseline liver function status before silver use.
A deep dive into future therapies for microcytic anemias and clinical considerations
Published in Expert Review of Hematology, 2023
François Rodrigues, Tereza Coman, Guillemette Fouquet, Francine Côté, Geneviève Courtois, Thiago Trovati Maciel, Olivier Hermine
Another enzyme responsible for iron oxidation is ceruloplasmin, a copper transporter. Patients with aceruloplasminemia suffer from microcytic anemia due to low transferrin saturation since transferrin cannot be loaded with unoxidized iron. Aceruloplasminemia is also associated with iron accumulation in several tissues including the brain, caused by impaired deficient iron egress from cells [20,21].
Related Knowledge Centers
- Ataxia
- Blepharospasm
- Ceruloplasmin
- Chorea
- Dystonia
- Tremor
- Dementia
- Liver
- Dominance
- Neurodegeneration With Brain Iron Accumulation