Amyloid β and neuromelanin-Toxic or protective molecules?. The cellular context makes the difference

K. S J Rao, M. L. Hegde, S. Anitha, M. Musicco, F. A. Zucca, N. J. Turro, L. Zecca

Research output: Contribution to journalArticle

Abstract

Alzheimer's disease (AD) and Parkinson's disease (PD) share several pathological mechanisms. The parallels between amyloid beta (Aβ) in AD and α-synuclein in PD have been discussed in several reports. However, studies of the last few years show that Aβ also shares several important characteristics with neuromelanin (NM), whose role in PD is emerging. First, both molecules accumulate with aging, the greatest risk factor for AD and PD. Second, in spite of their different structures, Aβ and NM have similar characteristics that could also lead to neuroprotection. Metals are required to catalyze their formation and they can bind large amounts of these metals, generating stable complexes and thus playing a protective role against metal toxicity. Moreover, they may be able to remove toxic species such as oligopeptides and excess cytosolic dopamine. Third, both Aβ and NM have been implicated in parallel aspects of the neuronal death that underlies AD and PD, respectively. For example, both molecules can activate microglia, inducing release of toxic factors such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and nitric oxide (NO). A careful analysis of these parallel effects of Aβ and NM, including their seemingly paradoxical ability to participate in both cell death and protection, may lead to an improved understanding of the roles of these molecules in neurodegeneration and also provide insights into possible parallels in the pathological mechanisms underlying AD and PD.

Original languageEnglish
Pages (from-to)364-373
Number of pages10
JournalProgress in Neurobiology
Volume78
Issue number6
DOIs
Publication statusPublished - Apr 2006

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Keywords

  • Amyloid beta
  • Neurodegeneration
  • Neuromelanin

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Rao, K. S. J., Hegde, M. L., Anitha, S., Musicco, M., Zucca, F. A., Turro, N. J., & Zecca, L. (2006). Amyloid β and neuromelanin-Toxic or protective molecules?. The cellular context makes the difference. Progress in Neurobiology, 78(6), 364-373. https://doi.org/10.1016/j.pneurobio.2006.03.004