Alpha synuclein protein is involved in Aluminum-induced cell death and oxidative stress in PC12 cells

Saberzadeh, Jamileh; Arabsolghar, Rita; Takhshid, Mohammad Ali

doi:10.1016/j.brainres.2016.01.037

Cited by 30 publications

(13 citation statements)

References 37 publications

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“…In previous studies, two forms of aluminum chloride and Almal were used ( 21 22 23 ). Almal is a lipophilic complex and permeable to the cell membrane ( 24 ).…”

Section: Discussionmentioning

confidence: 99%

The protective effect of sodium benzoate on aluminum toxicity in PC12 cell line

et al. 2017

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Sodium benzoate (SB) is one of the food additives and preservatives that prevent the growth of fungi and bacteria. SB has been shown to improve the symptoms of neurodegenerative disease such as Alzheimer's disease. The aim of this study was to evaluate the effect of SB on the cell survival and cellular antioxidant indices after exposure to aluminum maltolate (Almal) in PC12 cell line as a model of neurotoxicity. The cells exposed to different concentrations of SB (0.125 to 3 mg/mL) in the presence of Almal (500 µM) and cell viability, the level of reactive oxygen species (ROS), glutathione content and catalase activity were measured. The results showed that low concentrations of SB caused an increase in the cell survival, but cell viability was reduced in high concentrations. SB could neither prevent the level of ROS production nor change glutathione content. SB (0.5 mg/mL) significantly increased the catalase enzyme activity as compared to the Almal. This study suggested that SB did not completely protect the cell to aluminum-induced free radicals toxicity. Possibly SB improves the symptoms of neurodegenerative disease by other mechanisms.

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“…In previous studies, two forms of aluminum chloride and Almal were used ( 21 22 23 ). Almal is a lipophilic complex and permeable to the cell membrane ( 24 ).…”

Section: Discussionmentioning

confidence: 99%

The protective effect of sodium benzoate on aluminum toxicity in PC12 cell line

et al. 2017

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“…Recently, it has been claimed that truncation of α‐synuclein, which promotes its aggregation, may occur through caspase‐1 activity . In this case, caspase‐1 is activated by classical activation of inflammasomes by stimuli such as nigericin, paraquat, aluminum crystals, or LPS …”

Section: Nlrp3 Inflammasome‐mediated Inflammatory Pathways In Pdmentioning

confidence: 99%

“…65 In this case, caspase-1 is activated by classical activation of inflammasomes by stimuli such as nigericin, paraquat, aluminum crystals, or LPS. 65,66 α-Synuclein can exist in the brain in 2 forms, monomeric and fibrillar. 67 In human primary monocytes, although both the fibrillar and monomeric forms of α-synuclein are capable of activating microglial expression of pro-IL-1β through interaction with TLR2, only the fibrillar form of α-synuclein is able to release mature IL-1β through activation of the NLRP3 inflammasome.…”

Section: Nlrp3 Inflammasome-mediated Inflammatory Pathways In Pdmentioning

confidence: 99%

Targeting the Microglial NLRP3 Inflammasome and Its Role in Parkinson's Disease

et al. 2019

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Excessive activation of microglia and subsequent release of proinflammatory cytokines play a crucial role in neuroinflammation and neurodegeneration in Parkinson's disease (PD). Components of the nucleotide‐binding oligomerization domain and leucine‐rich‐repeat‐ and pyrin‐domain‐containing 3 inflammasome complex, leucine‐rich‐repeat‐ and pyrin‐domain‐containing 3, caspase‐1, and apoptosis‐associated speck‐like protein containing a CARD, are highly expressed in activated microglia in PD patient brains. Findings suggest that neurotoxins, aggregation of α‐synuclein, mitochondrial reactive oxygen species, and disrupted mitophagy are the key regulators of microglial leucine‐rich‐repeat‐ and pyrin‐domain‐containing 3 inflammasome activation and release of interleukin‐1β and interleukin‐18 caspase‐1‐mediated pyroptotic cell death in the substantia nigra of the brain. Although this evidence suggests the leucine‐rich‐repeat‐ and pyrin‐domain‐containing 3 inflammasome may be a potential drug target for treatment of PD, the exact mechanism of how the microglia sense these stimuli and initiate leucine‐rich‐repeat‐ and pyrin‐domain‐containing 3 inflammasome signaling is unknown. Here, the molecular mechanism and regulation of microglial leucine‐rich‐repeat‐ and pyrin‐domain‐containing 3 inflammasome activation and its role in the pathogenesis of PD are discussed. Moreover, the potential of both endogenous and synthetic leucine‐rich‐repeat‐ and pyrin‐domain‐containing 3 inflammasome modulators, long noncoding RNA, microRNA to develop novel therapeutics to treat PD is presented. Overall, we recommend that the microglial leucine‐rich‐repeat‐ and pyrin‐domain‐containing 3 inflammasome can be a potential target for PD treatment. © 2019 International Parkinson and Movement Disorder Society

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“…One recent study [114] demonstrated a neurotoxic role for α-Syn in Al-mediated oxidative stress and cell death. Tsunemi et al [131] demonstrated that silencing PARK9 (putative cation transporter) leads to intracellular dyshomeostasis of Zn 2+ , causing lysosomal dysfunction and ultimately α-Syn accumulation.…”

Section: Metalsmentioning

confidence: 99%

Role of neurotoxicants and traumatic brain injury in α-synuclein protein misfolding and aggregation

Rokad

Ghaisas

Harischandra

et al. 2017

Brain Research Bulletin

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Protein misfolding and aggregation are key pathological features of many neurodegenerative diseases including Parkinson’s disease (PD) and other forms of human Parkinsonism. PD is a complex and multifaceted disorder whose etiology is not fully understood. However, several lines of evidence support the multiple hit hypothesis that genetic vulnerability and environmental toxicants converge to trigger PD pathology. Alpha-synuclein (α-Syn) aggregation in the brain is an important pathophysiological characteristic of synucleinopathies including PD. Epidemiological and experimental studies have shown that metals and pesticides play a crucial role in α-Syn aggregation leading to the onset of various neurodegenerative diseases including PD. In this review, we will emphasize key findings of several epidemiological as well as experimental studies of metal- and pesticide-induced α-Syn aggregation and neurodegeneration. We will also discuss other factors such as traumatic brain injury and oxidative insult in the context of α-Syn-related neurodegenerative processes.

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Alpha synuclein protein is involved in Aluminum-induced cell death and oxidative stress in PC12 cells

Cited by 30 publications

References 37 publications

The protective effect of sodium benzoate on aluminum toxicity in PC12 cell line

The protective effect of sodium benzoate on aluminum toxicity in PC12 cell line

Targeting the Microglial NLRP3 Inflammasome and Its Role in Parkinson's Disease

Role of neurotoxicants and traumatic brain injury in α-synuclein protein misfolding and aggregation

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