The Pivotal Role of Copper in Neurodegeneration: A New Strategy for the Therapy of Neurodegenerative Disorders

Mol Pharm. 2018 Mar 5;15(3):808-820. doi: 10.1021/acs.molpharmaceut.7b00841. Epub 2018 Feb 2.

Abstract

Copper is an essential trace element for the human body since it is a cofactor of several enzymes and proteins and plays a pivotal role in several biological functions (e.g., respiration, protection from oxidative damage, iron metabolism, etc.), also including the central nervous system development and functioning (e.g., synthesis of neurotransmitters, myelination, activation of neuropeptides, etc.). Therefore, copper dysmetabolism is associated with different toxic effects, mainly represented by oxidative stress, and it has been reported in many neurodegenerative disorders, such as Wilson's disease, Menkes disease, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This paper shows a detailed report of how copper is involved in the pathophysiology of these diseases. Moreover, a hint on novel therapeutic approaches based on restoring copper homeostasis through metal chelators will be pointed out.

Keywords: copper; metal chelators; natural compounds; neurodegenerative diseases; oxidative stress.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain Chemistry / drug effects*
  • Chelating Agents / pharmacology
  • Chelating Agents / therapeutic use*
  • Copper / metabolism
  • Copper / toxicity*
  • Copper-Transporting ATPases / genetics
  • Copper-Transporting ATPases / metabolism
  • Disease Models, Animal
  • Humans
  • Neurodegenerative Diseases / drug therapy*
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / pathology
  • Oxidative Stress / drug effects
  • Superoxide Dismutase-1 / genetics
  • Superoxide Dismutase-1 / metabolism

Substances

  • Chelating Agents
  • SOD1 protein, human
  • Copper
  • Superoxide Dismutase-1
  • Copper-Transporting ATPases