Metal Imbalance in Neurodegenerative Diseases with a Specific Concern to the Brain of Multiple Sclerosis Patients

Abstract

There is increasing evidence that deregulation of metals contributes to a vast range of neurodegenerative diseases including multiple sclerosis (MS). MS is a chronic inflammatory disease of the central nervous system (CNS) manifesting disability and neurological symptoms. The precise origin of MS is unknown, but the disease is characterized by focal inflammatory lesions in the CNS associated with an autoimmune reaction against myelin. The treatment of this disease has mainly been based on the prescription of immunosuppressive and immune-modulating agents. However, the rate of progressive disability and early mortality is still worrisome. Metals may represent new diagnostic and predictive markers of severity and disability as well as innovative candidate drug targets for future therapies. In this review, we describe the recent advances in our understanding on the role of metals in brain disorders of neurodegenerative diseases and MS patients.

Acetylcholinesterase Inhibitors in the Treatment of Neurodegenerative Diseases and the Role of Acetylcholinesterase in their Pathogenesis

“…This confirms the significant role of the enzyme in the pathogenesis of SM. SM patients also have reduced manganese levels in PMR compared to controls [154,155]. Moreover, high concentrations of this element have an inhibitory effect on AChE [156].…”

Microalgae as Potential Sources of Bioactive Compounds for Functional Foods and Pharmaceuticals

“…[45] are acknowledged as Generally Recognized as Safe by the Food and Drug Administration and are also being investigated as bioremediation agents of heavy metals (copper, cadmium, iron, among others), due to their affinity towards metal ions. Although metals are vital for the normal functioning of the human body, an imbalance of metals in the biological matrix is known to generate free radicals through the Fenton and Haber-Weiss reactions and are often implicated in neurodegenerative diseases [6,46]. Chelation mainly occurs when a ligand (e.g., cyclic peptides, ionophores, siderophores, phytochelatins, flavonoids) has at least two donor groups, which link to a central metal atom/ion through an acyclic or ring-like coordination bond and form stable complexes [47].…”

“…When inflammation is prolonged over time, chronic inflammation sets in, and dysregulated inflammation has been identified in the genesis of almost all types of human diseases or disorders such as cancer, neurodegenerative disorders, multiple sclerosis, diabetes, atherosclerosis, arthritis, and cardiovascular diseases [4,5]. Deregulation of metal homeostasis is another component that contributes to illness development, especially in neurodegenerative diseases, as the accumulation of hazardous redox metals in the body can result in neuron degeneration, cell damage, loss, and death [6]. Redox-active metals have been linked to oxidative stress due to the Fenton and Haber-Weiss reactions, which produce reactive oxygen and nitrogen species, further increasing oxidative stress [7], which is especially dramatic considering that the brain is the organ with highest oxygen consumption [8].…”

The position of geochemical variables as causal co-factors of diseases of unknown aetiology

“…Binding of metals to the bases usually disrupts base pair hydrogen bonding and destabilises the double helix (Anastassopoulou [ 279 ]). Research on the role of DNA-bound metal ions in the incidence of certain DUA such as the neurogenerative diseases (e.g., AD, PD and MS) has been going on with increased intensity in the last two decades (See, e.g., Anastassopoulou [ 279 ]; Dales and Desplat-Jégo [ 280 ]; Morris, Jr. [ 281 ]; Hasani Nourian et al [ 282 ]), but exact pathways and mechanisms by which metal toxicity is induced are still not fully understood . (Ibrahim and Gabr [ 283 ]) and a number of other authors consider it likely that each metal could be toxic through specific pathways and mechanisms (See Fig.…”