Toxic Feedback Loop Involving Iron, Reactive Oxygen Species, α-Synuclein and Neuromelanin in Parkinson’s Disease and Intervention with Turmeric

Rensburg, Zuné Jansen van; Abrahams, Shameemah; Bardien, Soraya; Kenyon, Colin

doi:10.1007/s12035-021-02516-5

Cited by 28 publications

(19 citation statements)

References 193 publications

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“…ROS is considered to be an important killer of body health, accelerating the catalysis of neurological diseases (including PD), and its activation can disrupt the balance of redox levels . Growing studies had shown that the production of ROS aggravates the misfolding of α-SYN in the brain and leads to the occurrence of PD and other synucleinopathies. , In clinical trials, probiotics reduced the production of α-SYN aggregates by inhibiting the ROS level and finally alleviated the condition of patients with PD . In addition, L.…”

Section: Discussionmentioning

confidence: 99%

Lactobacillus plantarum DP189 Reduces α-SYN Aggravation in MPTP-Induced Parkinson’s Disease Mice via Regulating Oxidative Damage, Inflammation, and Gut Microbiota Disorder

Wang

Zhao

et al. 2022

J. Agric. Food Chem.

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This study aimed to evaluate the attenuating effect of Lactobacillus plantarum DP189 on α-synuclein (α-SYN) aggregates in the substantia nigra (SN) of Parkinson's disease (PD) mice via 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)induced. Our results indicated that L. plantarum DP189 increased the levels of superoxide dismutase (SOD), glutathione peroxide (GSH-Px), and interleukin-10 (IL-10) and decreased the levels of malondialdehyde (MDA), reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β). Moreover, L. plantarum DP189 reduced the α-SYN accumulation in SN. Mechanistically, L. plantarum DP189 activated the expression of nuclear factor erythroid 2-related factor (Nrf2)/ARE and PGC-1α pathways and suppressed the NLRP3 inflammasome. Furthermore, fecal analysis showed that L. plantarum DP189 reshaped the gut microbiota in PD mice by reducing the number of pathogenic bacteria (Proteobacteria and Actinobacteria) and increased the abundance of probiotics (Lactobacillus and Prevotella). Our results suggested that L. plantarum DP189 could delay the neurodegeneration caused by the accumulation of α-SYN in the SN of PD mice via suppressing oxidative stress, repressing proinflammatory response, and modulating gut microbiota.

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Section: Discussionmentioning

confidence: 99%

Lactobacillus plantarum DP189 Reduces α-SYN Aggravation in MPTP-Induced Parkinson’s Disease Mice via Regulating Oxidative Damage, Inflammation, and Gut Microbiota Disorder

Wang

Zhao

et al. 2022

J. Agric. Food Chem.

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“…α-synuclein can in turn increase ROS and iron by inducing mitochondrial dysfunction and iron reductase activity. These effects are transmitted to neighboring neurons in a toxic feedback loop, which leads to PD pathology [ 126 ].…”

Section: Iron Metabolism and Neurodegenerative Diseasesmentioning

confidence: 99%

Iron Metabolism in Aging and Age-Related Diseases

Tian

Yuan

et al. 2022

IJMS

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Iron is a trace metal element necessary to maintain life and is also involved in a variety of biological processes. Aging refers to the natural life process in which the physiological functions of the various systems, organs, and tissues decline, affected by genetic and environmental factors. Therefore, it is imperative to investigate the relationship between iron metabolism and aging-related diseases, including neurodegenerative diseases. During aging, the accumulation of nonheme iron destroys the stability of the intracellular environment. The destruction of iron homeostasis can induce cell damage by producing hydroxyl free radicals, leading to mitochondrial dysfunction, brain aging, and even organismal aging. In this review, we have briefly summarized the role of the metabolic process of iron in the body, then discussed recent developments of iron metabolism in aging and age-related neurodegenerative diseases, and finally, explored some iron chelators as treatment strategies for those disorders. Understanding the roles of iron metabolism in aging and neurodegenerative diseases will fill the knowledge gap in the field. This review could provide new insights into the research on iron metabolism and age-related neurodegenerative diseases.

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“…There is growing evidence of a relationship between ROS, ferroptosis, and PD. Therefore, it can be suggested that VDAC3 is associated with ROS or/and ferroptosis [ 99 ]. So far, the structural framework of VDAC3 has not yet been discovered [ 100 ].…”

Section: Vdac3 and Pdmentioning

confidence: 99%

The Potential Role of Voltage-Dependent Anion Channel in the Treatment of Parkinson’s Disease

Wang

Yang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Parkinson’s disease (PD) is a neurodegenerative disease second only to Alzheimer’s disease in terms of prevalence. Previous studies have indicated that the occurrence and progression of PD are associated with mitochondrial dysfunction. Mitochondrial dysfunction is one of the most important causes for apoptosis of dopaminergic neurons. Therefore, maintaining the stability of mitochondrial functioning is a potential strategy in the treatment of PD. Voltage-dependent anion channel (VDAC) is the main component in the outer mitochondrial membrane, and it participates in a variety of biological processes. In this review, we focus on the potential roles of VDACs in the treatment of PD. We found that VDACs are involved in PD by regulating apoptosis, autophagy, and ferroptosis. VDAC1 oligomerization, VDACs ubiquitination, regulation of mitochondrial permeability transition pore (mPTP) by VDACs, and interaction between VDACs and α-synuclein (α-syn) are all promising methods for the treatment of PD. We proposed that inhibition of VDAC1 oligomerization and promotion of VDAC1 ubiquitination as an effective approach for the treatment of PD. Previous studies have proven that the expression of VDAC1 has a significant change in PD models. The expression levels of VDAC1 are decreased in the substantia nigra (SN) of patients suffering from PD compared with the control group consisting of normal individuals by using bioinformatics tools. VDAC2 is involved in PD mainly through the regulation of apoptosis. VDAC3 may have a similar function to VDAC1. It can be concluded that the functional roles of VDACs contribute to the therapeutic strategy of PD.

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Toxic Feedback Loop Involving Iron, Reactive Oxygen Species, α-Synuclein and Neuromelanin in Parkinson’s Disease and Intervention with Turmeric

Cited by 28 publications

References 193 publications

Lactobacillus plantarum DP189 Reduces α-SYN Aggravation in MPTP-Induced Parkinson’s Disease Mice via Regulating Oxidative Damage, Inflammation, and Gut Microbiota Disorder

Lactobacillus plantarum DP189 Reduces α-SYN Aggravation in MPTP-Induced Parkinson’s Disease Mice via Regulating Oxidative Damage, Inflammation, and Gut Microbiota Disorder

Iron Metabolism in Aging and Age-Related Diseases

The Potential Role of Voltage-Dependent Anion Channel in the Treatment of Parkinson’s Disease

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