Abstract:
:A growing set of observations points to mitochondrial dysfunction, iron accumulation, oxidative damage and chronic inflammation as common pathognomonic signs of a number of neurodegenerative diseases that includes Alzheimer's disease, Huntington disease, amyotrophic lateral sclerosis, Friedrich's ataxia and Parkinson's disease. Particularly relevant for neurodegenerative processes is the relationship between mitochondria and iron. The mitochondrion upholds the synthesis of iron-sulfur clusters and heme, the most abundant iron-containing prosthetic groups in a large variety of proteins, so a fraction of incoming iron must go through this organelle before reaching its final destination. In turn, the mitochondrial respiratory chain is the source of reactive oxygen species (ROS) derived from leaks in the electron transport chain. The co-existence of both iron and ROS in the secluded space of the mitochondrion makes this organelle particularly prone to hydroxyl radical-mediated damage. In addition, a connection between the loss of iron homeostasis and inflammation is starting to emerge; thus, inflammatory cytokines like TNF-alpha and IL-6 induce the synthesis of the divalent metal transporter 1 and promote iron accumulation in neurons and microglia. Here, we review the recent literature on mitochondrial iron homeostasis and the role of inflammation on mitochondria dysfunction and iron accumulation on the neurodegenerative process that lead to cell death in Parkinson's disease. We also put forward the hypothesis that mitochondrial dysfunction, iron accumulation and inflammation are part of a synergistic self-feeding cycle that ends in apoptotic cell death, once the antioxidant cellular defense systems are finally overwhelmed.
journal_name
Front Pharmacoljournal_title
Frontiers in pharmacologyauthors
Urrutia PJ,Mena NP,Núñez MTdoi
10.3389/fphar.2014.00038subject
Has Abstractpub_date
2014-03-10 00:00:00pages
38issn
1663-9812journal_volume
5pub_type
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journal_title:Frontiers in pharmacology
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doi:10.3389/fphar.2014.00054
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abstract::Background: Shexiang Baoxin Pill (SBP) is a well-known composite formula of traditional Chinese medicine (TCM), which is commonly used today in treating cardiovascular diseases. SBP consists of seven materials thereof, including Moschus, extract of Ginseng Radix et Rhizoma, Bovis Calculus Artifactus, Cinnamomi Cortex,...
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abstract::Phytoestrogen has been proposed as an alternative to hormone replacement therapy, which has been demonstrated to promote a high risk of breast cancer. However, the effect of phytoestrogen on breast cancer development has not been fully understood. Bakuchiol is an active ingredient of a traditional Chinese herbal medic...
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abstract::Purpose: Asian populations have around 40-60% frequency of reduced function allele CYP2D6∗10 compared to 1-2% in Caucasian populations. The wide range of CYP2D6 enzyme activities in subjects with the CYP2D6∗10 variant is a big concern for clinical practice. The quantitative analysis measuring the impact of CYP2D6 enzy...
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pub_type: 杂志文章,评审
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journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2015.00250
更新日期:2015-10-29 00:00:00
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doi:10.3389/fphar.2018.01436
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pub_type: 杂志文章
doi:10.3389/fphar.2018.00918
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pub_type: 杂志文章
doi:10.3389/fphar.2020.00652
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pub_type: 杂志文章,评审
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journal_title:Frontiers in pharmacology
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doi:10.3389/fphar.2020.00681
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