The role of metals and their effect on oxidative stress in amyotrophic lateral sclerosis

Mauro Cozzolino, Maria Teresa Carrì

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Amyotrophic lateral sclerosis (ALS) is one of the most common neurodegenerative disorders occurring both as a sporadic disease (sALS) and in a familial form (fALS). A major breakthrough in deciphering the molecular mechanisms underlying ALS was provided in 1993 by the observation that mutations in the gene coding for the antioxidant enzyme Cu, Zn superoxide dismutase (SOD1) were found in one-fifth of fALS patients. Increasing evidence indicates that cellular functions are impaired as a consequence of the expression of mutant SOD1 (mutSOD1) converge on pathways that could be activated in sporadic ALS by other toxic factors. Loss of neurons in ALS results from a complex interplay of oxidative injury, excitotoxic stimulation, aggregation and dysfunction of critical proteins, and genetic factors. ALS is the result of a complex neurotoxic cascade that involves a molecular cross-talk between motor neurons and glia and between motor neurons and muscle. Oxidative stress (OS) may play a crucial role in this cascade, and many consistent observations support a role for metal-mediated OS as one of the mechanisms contributing to the pathogenesis of ALS. Intracellular metal-induced OS may be primed by many different mechanisms, including the presence of mutant SOD1, alterations in copper-handling and copper-responsive genes such as angiogenin and vascular endothelial growth factor (VEGF), and iron mishandling. This chapter focuses on existing evidence that metal-mediated OS is a culprit in the pathogenesis of ALS.

Original languageEnglish
Title of host publicationOxidative Stress and Neurodegenerative Disorders
PublisherElsevier
Pages383-398
Number of pages16
ISBN (Print)9780444528094
DOIs
Publication statusPublished - 2007

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'The role of metals and their effect on oxidative stress in amyotrophic lateral sclerosis'. Together they form a unique fingerprint.

Cite this