The Role of Metals Ions in Neurodegenerative Diseases

A special issue of Biomolecules (ISSN 2218-273X).

Deadline for manuscript submissions: 15 August 2024 | Viewed by 759

Special Issue Editor


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Guest Editor
Department of Inorganic and Analytical Chemistry, University of Debrecen, Debrecen, Hungary
Interests: copper; zinc; peptide histidine; speciation

Special Issue Information

Dear Colleagues,

Neurological disorders represent one of the major risks for the normal life of human society, especially among elderly people. Alzheimer’s disease and Parkinson’s disease are the most common and best studied forms of these disorders but a series of less frequent but very serious diseases (like Huntington’s disease, Wilson’s disease, ALS, PSP, etc.) belong also to this category. There are some common features of neurological disorders. Among them, abnormal conformational changes and/or the subsequent aggregation of specific proteins are the best known, but the involvement of various metal ions (mainly copper, iron, and zinc) in these processes is also widely suggested. A huge number of previous publications demonstrated the role of metal ion accumulation in the development of neurological disorders, either via direct complex formation or through the oxidative damage/cleavage of specific peptides or proteins. Unfortunately, effective therapy does not exist for the treatment or prevention of these diseases. Therefore, further studies are required on all aspects of the metal ion peptide–protein interaction and the results may significantly contribute to a better understanding of the development of neurological disorders.

In this Special Issue, manuscripts describing the molecular background of metal ion peptide–protein interactions are collected with a special emphasis on the copper, zinc, and iron complexes of the amyloid beta and peptide fragments of prion and Tau proteins. The results of biological and/or clinical studies are also invited. It is widely accepted that chelation therapy can be used for the treatment of certain forms of neurodegeneration and the submission of manuscripts related to this subject is also encouraged.

Prof. Dr. Imre Sòvágó
Guest Editor

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Keywords

  • Alzheimer’s disease
  • Parkinson’s disease
  • metal complexes
  • amyloid-beta
  • peptide fragments of prion and tau proteins

Published Papers (1 paper)

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Research

9 pages, 588 KiB  
Communication
Ischemic Neuroprotection by Insulin with Down-Regulation of Divalent Metal Transporter 1 (DMT1) Expression and Ferrous Iron-Dependent Cell Death
by Francesca Fenaroli, Alessandra Valerio and Rosaria Ingrassia
Biomolecules 2024, 14(7), 856; https://doi.org/10.3390/biom14070856 - 15 Jul 2024
Viewed by 426
Abstract
Background: The regulation of divalent metal transporter-1 (DMT1) by insulin has been previously described in Langerhans cells and significant neuroprotection was found by insulin and insulin-like growth factor 1 treatment during experimental cerebral ischemia in acute ischemic stroke patients and in a rat [...] Read more.
Background: The regulation of divalent metal transporter-1 (DMT1) by insulin has been previously described in Langerhans cells and significant neuroprotection was found by insulin and insulin-like growth factor 1 treatment during experimental cerebral ischemia in acute ischemic stroke patients and in a rat 6-OHDA model of Parkinson’s disease, where DMT1 involvement is described. According to the regulation of DMT1, previously described as a target gene of NF-kB in the early phase of post-ischemic neurodegeneration, both in vitro and in vivo, and because insulin controls the NFkB signaling with protection from ischemic cell death in rat cardiomyocytes, we evaluated the role of insulin in relation to DMT1 expression and function during ischemic neurodegeneration. Methods: Insulin neuroprotection is evaluated in differentiated human neuroblastoma cells, SK-N-SH, and in primary mouse cortical neurons exposed to oxygen glucose deprivation (OGD) for 8 h or 3 h, respectively, with or without 300 nM insulin. The insulin neuroprotection during OGD was evaluated in both cellular models in terms of cell death, and in SK-N-SH for DMT1 protein expression and acute ferrous iron treatment, performed in acidic conditions, known to promote the maximum DMT1 uptake as a proton co-transporter; and the transactivation of 1B/DMT1 mouse promoter, already known to be responsive to NF-kB, was analyzed in primary mouse cortical neurons. Results: Insulin neuroprotection during OGD was concomitant to the down-regulation of both DMT1 protein expression and 1B/DMT1 mouse promoter transactivation. We also showed the insulin-dependent protection from cell death after acute ferrous iron treatment. In conclusion, although preliminary, this evaluation highlights the peculiar role of DMT1 as a possible pharmacological target, involved in neuroprotection by insulin during in vitro neuronal ischemia and acute ferrous iron uptake. Full article
(This article belongs to the Special Issue The Role of Metals Ions in Neurodegenerative Diseases)
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