astaxanthine and Parkinson-Disease

Parkinson's disease is the second most common neurodegenerative movement disorder; however, its etiology remains elusive. Nevertheless, in vivo observations have concluded that oxidative stress is one of the most common causes in the pathogenesis of Parkinson's disease. It is known that mitochondria play a crucial role in reactive oxygen species-mediated pathways, and several gene products that associate with mitochondrial function are the subject of Parkinson's disease research. The PTEN-induced kinase 1 (PINK1) protects cells from mitochondrial dysfunction and is linked to the autosomal recessive familial form of the disease. PINK1 is a key player in many signaling pathways engaged in mitophagy, apoptosis, or microglial inflammatory response and is induced by oxidative stress. Several proteins participate in mitochondrial networks, and they are associated with PINK1. The E3 ubiquitin ligase Parkin, the protease presenilin-associated rhomboid-like serine protease, the tyrosine kinase c-Abl, the protein kinase MARK2, the protease HtrA2, and the tumor necrosis factor receptor-associated protein 1 (TRAP1) provide different steps of control in protection against oxidative stress. Furthermore, environmental toxins, such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, have been identified as contributors to parkinsonism by increasing oxidative stress in dopaminergic neurons. The present review discusses the mechanisms and effects of oxidative stress, the emerging concept of the impact of environmental toxins, and a possible neuroprotective role of the antioxidant astaxanthin in various neurodegenerative disorders with particular emphasis in Parkinson's disease.

Topics: Animals; Apoptosis; Basal Ganglia; Calcium Signaling; Dopaminergic Neurons; Drosophila melanogaster; Drosophila Proteins; Humans; Metalloproteases; Metals, Heavy; Microglia; Mitochondria; Mitochondrial Proteins; Models, Neurological; Neuroprotective Agents; Neurotoxins; Oxidative Stress; Parkinson Disease; Parkinsonian Disorders; Protein Kinases; Proto-Oncogene Proteins c-abl; Receptors, Glutamate; Signal Transduction; Ubiquitin-Protein Ligases; Xanthophylls

Rotenone is a widely used organic pesticide that induces neurotoxicity via inhibition of mitochondrial complex I and oxidative stress actions for the most of dopaminergic neurons as that occurring in Parkinsonism disease (PD). Astaxanthin (ASX) is a natural pigment (carotenoids) and a potent therapeutic compound due to its antioxidant and anti-inflammatory properties. The commercially important cephalopod Doryteuthis singhalensis is widely distributed in tropical and subtropical waters in World Ocean. D. singhalensis is an important source of astaxanthin that contains valuable biological active compounds with many valuable pharmacological effects. The present study evaluated the effect of astaxanthin in preventing rotenone-induced toxicity of SK-N-SH human neuroblastoma cells in an in vitro model of experimental Parkinsonism. The results revealed the strongly significant antioxidant capability of extracted squid astaxanthin in 1,1- diphenyl- 2- picrylhydrazyl (DPPH) radical scavenging activity. In addition, astaxanthin treatment based on dose dependent manner significantly attenuated rotenone induced cytotoxicity, mitochondrial dysfunction and oxidative stress in SKN- SH cells. It is concluded that the marine squid derived astaxanthin could be used as a potential neuroprotector against rotenone induced toxicity due to its antioxidant, and anti-apoptotic properties. Consequently, it could be a supportive remedy for neurodegenerative diseases like Parkinson's disease.

Topics: Animals; Antioxidants; Decapodiformes; Humans; Neuroprotective Agents; Neurotoxicity Syndromes; Oxidative Stress; Parkinson Disease; Parkinsonian Disorders; Rotenone

Parkinson's disease (PD) is the second largest neurodegenerative disorder caused by the decreased number of dopaminergic (DAc) neurons in the substantia nigra pars compacta (SNpc). There is evidence that oxidative stress can contribute degeneration of DAc neurons in SNpc which is mainly caused by apoptotic cell death. Thus, suppressing oxidative stress and apoptosis of DAc neurons is an effective strategy to mitigate the progress of PD. Astaxanthin (AST) is a carotenoid, which mainly exists in marine organisms and is a powerful biological antioxidant. In this study, we aimed to determine the neuroprotective effect of AST on paraquat (PQ) -induced models of PD in vitro and in vivo. Here, we showed that AST significantly enhanced cell survival of SH-SY5Y cells against PQ toxicity by suppressing apoptotic cell death and oxidative stress. Moreover, we found that AST significantly ameliorated PQ-induced behavioral disorders associated with PD in C57BL/6 J mice and the damage to DAc neurons in the SNpc of mice. Lastly, we found that the neuroprotective effects of AST were conducted through inhibiting PQ-induced activation of MAPK signaling. In conclusion, our study indicates that AST had a strong protective effect on PQ-induced oxidative stress and antagonized apoptotic cell death in SH-SY5Y cells and PQ-induced mice PD model, which might provide new insights of AST for PD treatment.

Topics: Animals; Disease Models, Animal; Dopaminergic Neurons; Humans; Mice; Mice, Inbred C57BL; Neuroblastoma; Paraquat; Parkinson Disease

Parkinson's disease (PD) is a common neurodegenerative disorder that featured by the loss of dopaminergic neurons. Astaxanthin (AST), an important antioxidant, is demonstrated to be a neuroprotective agent for PD. However, the underlying mechanisms of AST in PD remain largely unclear. In this study, we found that AST treatment significantly not only abolished the cell viability inhibition and apoptosis promotion induced by 1-methyl-4-phenylpyridinium (MPP+) in SH-SY5Y cells via inhibiting endoplasmic reticulum (ER) stress, but also reversed the MPP+ caused dysregulation of miR-7 and SNCA expression. MiR-7 knockdown and SNCA overexpression were achieved by treating SH-SY5Y cells with miR-7 inhibitor and pcDNA3.1-SNCA plasmids, respectively. MiR-7 could bind to and negatively regulate SNCA in SH-SY5Y cells. Treated SH-SY5Y cells with miR-7 inhibitor or pcDNA3.1-SNCA abrogated the protective effects of AST on MPP+ induced cytotoxicity. Knockdown of miR-7 aggravated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced neuron injury in vivo suggested by athletic performance, histopathological morphology, expression of tyrosine hydroxylase (TH) and TUNEL positvie cells, however, AST treatment could reverse these effects of miR-7 knockdown. Collectively, AST suppressed ER stress and protected against PD-caused neuron damage by targeting miR-7/SNCA axis, implying that AST might be a potential effective therapeutic agent for PD.

Topics: alpha-Synuclein; Apoptosis; Cell Line, Tumor; Endoplasmic Reticulum Stress; Humans; MicroRNAs; Parkinson Disease; Xanthophylls

Non-esterified astaxanthin (AST) has been reported to exhibit protective effects from Parkinson's disease (PD). Notably, DHA-acylated astaxanthin ester (DHA-AST) is widely distributed in the seafood. However, whether DHA-AST has an effect on PD, and the differences between DHA-AST, non-esterified AST and the combination of non-esterified AST (AST) with DHA (DHA + AST) is unclear. In the present study, mice with PD, induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), were employed to investigate the effects of DHA-AST, AST and DHA + AST on Parkinson's disease. The rotarod test results showed that DHA-AST significantly suppressed the PD development in MPTP-induced mice, and was better than the effects of AST and DHA + AST. Further mechanistic studies indicated that all three astaxanthin supplements could inhibit oxidative stress in the brain. It was noted that DHA-AST had the best ability to suppress the apoptosis of dopaminergic neurons via the mitochondria-mediated pathway and JNK and P38 MAPK pathway in the brain among the three treated groups. DHA-AST was superior to AST in preventing behavioral deficits coupled with apoptosis rather than oxidative stress, and might provide a valuable reference for the prevention and treatment of neurodegenerative diseases.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Apoptosis; Brain; Disease Models, Animal; Docosahexaenoic Acids; Dopaminergic Neurons; Esters; Male; Mice; Mice, Inbred C57BL; Neuroprotective Agents; Oxidative Stress; Parkinson Disease; Xanthophylls

Air pollution has become one of the most serious issues for human health and has been shown to be particularly concerning for neural and cognitive health. Recent studies suggest that fine particulate matter of less than 2.5 (PM2.5), common in air pollution, can reach the brain, potentially resulting in the development and acceleration of various neurological disorders including Alzheimer's disease, Parkinson's disease, and other forms of dementia, but the underlying pathological mechanisms are not clear. Astaxanthin is a red-colored phytonutrient carotenoid that has been known for anti-inflammatory and neuroprotective effects. In this study, we demonstrated that exposure to PM2.5 increases the neuroinflammation, the expression of proinflammatory M1, and disease-associated microglia (DAM) signature markers in microglial cells, and that treatment with astaxanthin can prevent the neurotoxic effects of this exposure through anti-inflammatory properties. Diesel particulate matter (Sigma-Aldrich) was used as a fine particulate matter 2.5 in the present study. Cultured rat glial cells and BV-2 microglial cells were treated with various concentrations of PM2.5, and then the expression of various inflammatory mediators and signaling pathways were measured using qRT-PCR and Western blot. Astaxanthin was then added and assayed as above to evaluate its effects on microglial changes, inflammation, and toxicity induced by PM2.5. PM2.5 increased the production of nitric oxide and reactive oxygen species and upregulated the transcription of various proinflammatory markers including Interleukin-1β (IL-1β), Interleukin-6 (IL-6), Tumor necrosis factor α (TNFα), inducible nitric oxide synthase (iNOS), triggering receptor expressed on myeloid cells 2 (TREM2), Toll-like receptor 2/4 (TLR2/4), and cyclooxygenase-2 (COX-2) in BV-2 microglial cells. However, the mRNA expression of IL-10 and arginase-1 decreased following PM2.5 treatment. PM2.5 treatment increased c-Jun N-terminal kinases (JNK) phosphorylation and decreased Akt phosphorylation. Astaxanthin attenuated these PM2.5-induced responses, reducing transcription of the proinflammatory markers iNOS and heme oxygenase-1 (HO-1), which prevented neuronal cell death. Our results indicate that PM2.5 exposure reformulates microglia via proinflammatory M1 and DAM phenotype, leading to neurotoxicity, and the fact that astaxanthin treatment can prevent neurotoxicity by inhibiting transition to the proinflammatory M1 and DAM phenotyp

Topics: Air Pollution; Alzheimer Disease; Animals; Anti-Inflammatory Agents; Cyclooxygenase 2; Gasoline; Gene Expression Regulation; Humans; Inflammation; Interleukin-1beta; Microglia; Neuroprotective Agents; NF-kappa B; Nitric Oxide Synthase Type II; Parkinson Disease; Particulate Matter; Proto-Oncogene Proteins c-akt; Rats; Xanthophylls

To investigate astaxanthin (ATX) neuroprotection, and its mechanism, on a 1-methyl-4-phenyl-pyridine ion (MPP+)-induced cell model of Parkinson's disease.. Mature, differentiated PC12 cells treated with MPP+ were used as an in vitro cell model. The MTT assay was used to investigate cell viability after ATX treatment, and western blot analysis was used to observe Sp1 (activated transcription factor 1) and NR1 (NMDA receptor subunit 1) protein expression, real-time PCR was used to monitor Sp1 and NR1 mRNA, and cell immunofluorescence was used to determine the location of Sp1 and NR1 protein and the nuclear translocation of Sp1.. PC12 cell viability was significantly reduced by MPP+ treatment. The expression of Sp1 and NR1 mRNA and protein were increased compared with the control (p < 0.01). Following co-treatment with ATX and MPP+, cell viability was significantly increased, and Sp1 and NR1 mRNA and protein were decreased, compared with the MPP+ groups (p < 0.01). In addition, mithracycin A protected PC12 cells from oxidative stress caused by MPP+ by specifically inhibiting the expression of Sp1. Moreover, cell immunofluorescence revealed that ATX could suppress Sp1 nuclear transfer.. ATX inhibited oxidative stress induced by MPP+ in PC12 cells, via the SP1/NR1 signaling pathway.

Topics: 1-Methyl-4-phenylpyridinium; Animals; Blotting, Western; Fluorescent Antibody Technique; Neuroprotective Agents; Oxidative Stress; Parkinson Disease; PC12 Cells; Plicamycin; Rats; Real-Time Polymerase Chain Reaction; Receptors, N-Methyl-D-Aspartate; RNA, Messenger; Signal Transduction; Sp1 Transcription Factor; Xanthophylls

Advances in understanding the neurodegenerative pathologies are creating new opportunities for the development of neuroprotective therapies, such as antioxidant food factors, lifestyle modification and drugs. However, the biomarker by which the effect of the agent on neurodegeneration is determined is limited. We here address hexanoyl dopamine (HED), one of novel dopamine adducts derived from brain polyunsaturated acid, referring to its in vitro formation, potent toxicity to SH-SY5Y cells, and application to assess the neuroprotective effect of antioxidative food factors. Dopamine is a neurotransmitter, and its deficiency is a characterized feature in Parkinson's disease (PD); thus, HED provides a new insight into the understanding of dopamine biology and pathophysiology of PD and a novel biomarker for the assessment of neuroprotective therapies. We have established an analytical system for the detection of HED and its toxicity to the neuroblstoma cell line, SH-SY5Y cells. Here, we discuss the characteristics of the system and its applications to investigate the neuroprotective effect of several antioxidants that originate from food.

Topics: Antioxidants; Cell Line, Tumor; Cell Survival; Chromatography, High Pressure Liquid; Curcumin; Dioxoles; Dopamine; Humans; Lignans; Neuroblastoma; Parkinson Disease; Tandem Mass Spectrometry; Tocopherols; Tocotrienols; Xanthophylls

Advances in understanding the neurodegenerative pathologies are creating new opportunities for the development of neuroprotective therapies, such as antioxidant food factors, lifestyle modification, and drugs. However, the biomarker by which to determine the effect of the agent on neurodegeneration is limited. We here address hexanoyl dopamine (HED), one of novel dopamine adducts derived from brain polyunsaturated acid, referring to its in vitro formation, potent toxicity to SH-SY5Y cells, and application to assess the neuroprotective effect of antioxidative food factors. Dopamine is a neurotransmitter and its deficiency is a characterized feature in Parkinson's disease (PD), thereby HED represents a new addition to understanding of dopamine biology and pathophysiology of PD and a novel biomarker for the assessment of neuroprotective therapies. We have established an analytical system using for the detection of HED and its toxicity to the neuroblstoma cell line, SH-SY5Y cells. Here, we discuss the characteristics of the system and its applications to investigate the neuroprotective effect of several antioxidants that originate from food.

Topics: Antioxidants; Cell Line, Tumor; Cell Survival; Chromatography, High Pressure Liquid; Curcumin; Dioxoles; Dopamine; Food; Humans; Lignans; Neuroprotective Agents; Oxidative Stress; Parkinson Disease; Tandem Mass Spectrometry; Tocopherols; Tocotrienols; Xanthophylls