Iron metabolism in the CNS: implications for neurodegenerative diseases

The involvement of the nervous system in the pathological process that occurs when COVID-19 is infected is becoming more and more obvious. The question of the possibility of the debut or progression of the already developed Parkinsonism syndrome in patients who have undergone COVID-19 is regularly raised. A large number of hypotheses are put forward to explain this relationship. It is assumed that a violation of iron metabolism in the brain may underlie the development and progression of neurodegenerative diseases, including after the new coronavirus infection SARS-CoV-2. The analysis of stu dies on the possible influence of iron metabolism disorders on the occurrence and mechanism of development of neurodegenerative diseases after infection with SARS-CoV-2 has been carried out. The processes of physiological maintenance of iron homeostasis, as well as the influence of physiological aging on the accumulation of iron in the central nervous system are described. The relationship between hyperferritinemia occurring in COVID-19 and ferroptosis as the basis of the neurodegenerative process in Parkinsons disease and Alzheimers disease is discussed. The main molecular mechanisms involved in ferroptosis are described. Examples of involvement of metal homeostasis disorders in the process of altering the structure of -synuclein, synthesis of -amyloid, hyperphosphorylated tau- protein are given. The causes of excessive iron accumulation in certain brain structures are discussed. The question of the possibility of using the assessment of changes in iron metabolism as a new biomarker of the progression of Parkinsons disease is analyzed. (1 figure, bibliography: 62 refs)

Download Full-text

Does Ceruloplasmin Defend Against Neurodegenerative Diseases?

Current Neuropharmacology ◽

10.2174/1570159x16666180508113025 ◽

2019 ◽

Vol 17 (6) ◽

pp. 539-549 ◽

Cited By ~ 16

Author(s):

Bo Wang ◽

Xiao-Ping Wang

Keyword(s):

Neurodegenerative Diseases ◽

Iron Metabolism ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Genetic Disorder ◽

Protective Role ◽

The Body ◽

Iron Accumulation ◽

Ferroxidase Activity ◽

Abnormal Metabolism

Ceruloplasmin (CP) is the major copper transport protein in plasma, mainly produced by the liver. Glycosylphosphatidylinositol-linked CP (GPI-CP) is the predominant form expressed in astrocytes of the brain. A growing body of evidence has demonstrated that CP is an essential protein in the body with multiple functions such as regulating the homeostasis of copper and iron ions, ferroxidase activity, oxidizing organic amines, and preventing the formation of free radicals. In addition, as an acute-phase protein, CP is induced during inflammation and infection. The fact that patients with genetic disorder aceruloplasminemia do not suffer from tissue copper deficiency, but rather from disruptions in iron metabolism shows essential roles of CP in iron metabolism rather than copper. Furthermore, abnormal metabolism of metal ions and oxidative stress are found in other neurodegenerative diseases, such as Wilson’s disease, Alzheimer’s disease and Parkinson’s disease. Brain iron accumulation and decreased activity of CP have been shown to be associated with neurodegeneration. We hypothesize that CP may play a protective role in neurodegenerative diseases. However, whether iron accumulation is a cause or a result of neurodegeneration remains unclear. Further research on molecular mechanisms is required before a consensus can be reached regarding a neuroprotective role for CP in neurodegeneration. This review article summarizes the main physiological functions of CP and the current knowledge of its role in neurodegenerative diseases.

Download Full-text

Mitochondrial iron metabolism and neurodegenerative diseases

NeuroToxicology ◽

10.1016/j.neuro.2021.11.003 ◽

2021 ◽

Author(s):

Ruiying Cheng ◽

Varun Dhorajia ◽

Jonghan Kim ◽

Yuho Kim

Keyword(s):

Neurodegenerative Diseases ◽

Iron Metabolism ◽

Mitochondrial Iron

Download Full-text

Pathogenetic aspects of hepcidin metabolism and ferrocinetics dysregulation in carbohydrate metabolism disorders

Diabetes Mellitus ◽

10.14341/dm9378 ◽

2019 ◽

Vol 21 (6) ◽

pp. 506-512 ◽

Cited By ~ 3

Author(s):

Tatiana V. Saprina ◽

Anastasia P. Zima ◽

Nadezhda N. Musina ◽

Tatiana S. Prokhorenko ◽

Alina V. Latypova ◽

...

Keyword(s):

Diabetes Mellitus ◽

Neurodegenerative Diseases ◽

Carbohydrate Metabolism ◽

Iron Metabolism ◽

Metabolic Disorders ◽

Ongoing Research ◽

Anaemia Of Chronic Disease ◽

Patients With Diabetes ◽

Parkinson Diseases

Hepcidin, a hormone regulating iron metabolism, has received attention for its role in the pathogenesis of dysregulations in carbohydrate metabolism. Hepcidin disorders in patients with diabetes mellitus are bi-directional: manifesting as iron overload syndrome in cases of decreased hepcidin production and as anaemia of chronic disease in cases of hepcidin hypersecretion. However, till date, detailed analyses of mechanisms underlying hepcidin dysregulation have not been conducted nor have the interactions of ferrocinetic and carbohydrate-metabolic disorders been examined. An association between diabetes mellitus and neurodegenerative diseases as well as the role of iron metabolism in Alzheimer or Parkinson diseases is a subject of ongoing research. This review provides a summary of the current understanding of hepcidin regulation and its disorders in various diseases, including diabetes mellitus and neurodegenerative diseases. In addition, we provide an overview of the available therapies that address ferrocinetic disorders resulting from the dysregulation of hepcidin.

Download Full-text

Autophagy and ageing: implications for age-related neurodegenerative diseases

Essays in Biochemistry ◽

10.1042/bse0550119 ◽

2013 ◽

Vol 55 ◽

pp. 119-131 ◽

Cited By ~ 37

Author(s):

Bernadette Carroll ◽

Graeme Hewitt ◽

Viktor I. Korolchuk

Keyword(s):

Neurodegenerative Diseases ◽

Energy Availability ◽

Future Studies ◽

Intracellular Degradation ◽

Age Related ◽

Autophagy Induction ◽

Social Importance ◽

Cellular Dysfunction ◽

Autophagy Activity ◽

Intense Research

Autophagy is a process of lysosome-dependent intracellular degradation that participates in the liberation of resources including amino acids and energy to maintain homoeostasis. Autophagy is particularly important in stress conditions such as nutrient starvation and any perturbation in the ability of the cell to activate or regulate autophagy can lead to cellular dysfunction and disease. An area of intense research interest is the role and indeed the fate of autophagy during cellular and organismal ageing. Age-related disorders are associated with increased cellular stress and assault including DNA damage, reduced energy availability, protein aggregation and accumulation of damaged organelles. A reduction in autophagy activity has been observed in a number of ageing models and its up-regulation via pharmacological and genetic methods can alleviate age-related pathologies. In particular, autophagy induction can enhance clearance of toxic intracellular waste associated with neurodegenerative diseases and has been comprehensively demonstrated to improve lifespan in yeast, worms, flies, rodents and primates. The situation, however, has been complicated by the identification that autophagy up-regulation can also occur during ageing. Indeed, in certain situations, reduced autophagosome induction may actually provide benefits to ageing cells. Future studies will undoubtedly improve our understanding of exactly how the multiple signals that are integrated to control appropriate autophagy activity change during ageing, what affect this has on autophagy and to what extent autophagy contributes to age-associated pathologies. Identification of mechanisms that influence a healthy lifespan is of economic, medical and social importance in our ‘ageing’ world.

Download Full-text

Nanotheranostic agents for neurodegenerative diseases

Emerging Topics in Life Sciences ◽

10.1042/etls20190141 ◽

2020 ◽

Vol 4 (6) ◽

pp. 645-675

Author(s):

Parasuraman Padmanabhan ◽

Mathangi Palanivel ◽

Ajay Kumar ◽

Domokos Máthé ◽

George K. Radda ◽

...

Keyword(s):

Drug Delivery ◽

Neurodegenerative Diseases ◽

Cell Types ◽

Specific Cell ◽

Ageing Population ◽

Target Tissue ◽

Therapeutic Approaches ◽

Surface Receptors ◽

Theranostic Agents ◽

Preclinical Animal Models

Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), affect the ageing population worldwide and while severely impairing the quality of life of millions, they also cause a massive economic burden to countries with progressively ageing populations. Parallel with the search for biomarkers for early detection and prediction, the pursuit for therapeutic approaches has become growingly intensive in recent years. Various prospective therapeutic approaches have been explored with an emphasis on early prevention and protection, including, but not limited to, gene therapy, stem cell therapy, immunotherapy and radiotherapy. Many pharmacological interventions have proved to be promising novel avenues, but successful applications are often hampered by the poor delivery of the therapeutics across the blood-brain-barrier (BBB). To overcome this challenge, nanoparticle (NP)-mediated drug delivery has been considered as a promising option, as NP-based drug delivery systems can be functionalized to target specific cell surface receptors and to achieve controlled and long-term release of therapeutics to the target tissue. The usefulness of NPs for loading and delivering of drugs has been extensively studied in the context of NDDs, and their biological efficacy has been demonstrated in numerous preclinical animal models. Efforts have also been made towards the development of NPs which can be used for targeting the BBB and various cell types in the brain. The main focus of this review is to briefly discuss the advantages of functionalized NPs as promising theranostic agents for the diagnosis and therapy of NDDs. We also summarize the results of diverse studies that specifically investigated the usage of different NPs for the treatment of NDDs, with a specific emphasis on AD and PD, and the associated pathophysiological changes. Finally, we offer perspectives on the existing challenges of using NPs as theranostic agents and possible futuristic approaches to improve them.

Download Full-text