Iron Redox Chemistry and Implications in the Parkinson's Disease Brain.

Autor: Abeyawardhane DL; Department of Chemistry, Virginia Commonwealth University, Richmond, VA 23284, USA., Lucas HR; Department of Chemistry, Virginia Commonwealth University, Richmond, VA 23284, USA.
Jazyk: angličtina
Zdroj: Oxidative medicine and cellular longevity [Oxid Med Cell Longev] 2019 Oct 09; Vol. 2019, pp. 4609702. Date of Electronic Publication: 2019 Oct 09 (Print Publication: 2019).
DOI: 10.1155/2019/4609702
Abstrakt: The etiology of Parkinson's disease (PD) is linked with cellular inclusions in the substantia nigra pars compacta region of the brain that are enriched in the misfolded presynaptic protein α -synuclein ( α S) and death of the dopaminergic neurons. Brain iron homeostasis governs both neurotransmission and neurodegeneration; hence, the role of iron in PD progression and neuronal health is apparent. Elevated iron deposits become prevalent in the cerebral region upon aging and even more so in the PD brain. Structural as well as oxidative modifications can result from coordination of α S with redox active iron, which could have functional and/or pathological implications. In this review, we will discuss iron-mediated α S aggregation, alterations in iron metabolism, and the role of the iron-dopamine couple. Moreover, iron interactions with N-terminally acetylated α S, the physiologically relevant form of the human protein, will be addressed to shed light on the current understanding of protein dynamics and the physiological environment in the disease state. Oxidative pathways and biochemical alterations resulting from aberrant iron-induced chemistry are the principal focus of this review in order to highlight the plethora of research that has uncovered this emerging dichotomy of iron playing both functional and disruptive roles in PD pathology.
Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper.
(Copyright © 2019 Dinendra L. Abeyawardhane and Heather R. Lucas.)
Databáze: MEDLINE
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