Spermine protects alpha-synuclein expressing dopaminergic neurons from manganese-induced degeneration

The natural polyamine spermidine and spermine have been reported to ameliorate aging and aging-induced dementia. However, the mechanism is still confused. An aging model, the senescence accelerated mouse-8 (SAMP8), was used in this study. Novel object recognition and the open field test results showed that oral administration of spermidine, spermine and rapamycin increased discrimination index, modified number, inner squares distance and times. Spermidine and spermine increased the activity of SOD, and decreased the level of MDA in the aging brain. Spermidine and spermine phosphorylate AMPK and regulate autophagy proteins (LC3, Beclin 1 and p62). Spermidine and spermine balanced mitochondrial and maintain energy for neuron, with the regulation of MFN1, MFN2, DRP1, COX IV and ATP. In addition, western blot results (Bcl-2, Bax and Caspase-3, NLRP3, IL-18, IL-1β) showed that spermidine and spermine prevented apoptosis and inflammation, and elevate the expression of neurotrophic factors, including NGF, PSD95and PSD93 and BDNF in neurons of SAMP8 mice. These results indicated that the effect of spermidine and spermine on anti-aging is related with improving autophagy and mitochondrial function.

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“…manner [56]. Autophagy is a self-eating mechanism and eliminates the aggregated protein and dysfunction organelles in autolysosomes [57].…”

Section: Agingmentioning

confidence: 99%

Spermidine and spermine delay brain aging by inducing autophagy in SAMP8 mice

Han

Zhao

et al. 2020

Aging

121

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“…Briefly, macrophages were seeded at 5 × 10 5 cells/well in. After incubation with siRNA, mitochondrial respiration was detected according to the manufacturer's instructions (Vijayan et al, 2019). Results were normalized to the actual cell count immediately after OCR recordings (Zhong et al, 2019).…”

Section: Cellular Respiration Assaysmentioning

confidence: 99%

Resveratrol Improves Bnip3-Related Mitophagy and Attenuates High-Fat-Induced Endothelial Dysfunction

Tan

et al. 2020

Front. Cell Dev. Biol.

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Statin treatment reduces cardiovascular risk. However, individuals with well-controlled low-density lipoprotein (LDL) levels may remain at increased risk owing to persistent high triglycerides and low high-density lipoprotein cholesterol. Because resveratrol promotes glucose metabolism and mitigates cardiovascular disorders, we explored its mechanism of protective action on high-fat-induced endothelial dysfunction. Human umbilical venous endothelial cells were treated with oxidized LDL (ox-LDL) in vitro. Endothelial function, cell survival, proliferation, migration, and oxidative stress were analyzed through western blots, quantitative polymerase chain reaction, ELISA, and immunofluorescence. ox-LDL induced endothelial cell apoptosis, proliferation arrest, and mobilization inhibition, all of which resveratrol reduced. ox-LDL suppressed the activities of mitochondrial respiration complex I and III and reduced levels of intracellular antioxidative enzymes, resulting in reactive oxygen species overproduction and mitochondrial dysfunction. Resveratrol treatment upregulated Bnip3-related mitophagy and prevented ox-LDL-mediated mitochondrial respiration complexes inactivation, sustaining mitochondrial membrane potential and favoring endothelial cell survival. We found that resveratrol enhanced Bnip3 transcription through hypoxia-inducible factor 1 (HIF1) and 5 AMP-activated protein kinase (AMPK). Inhibition of AMPK and HIF1 abolished resveratrol-mediated protection of mitochondrial redox balance and endothelial viability. Together, these data demonstrate resveratrol reduces hyperlipemiarelated endothelial damage by preserving mitochondrial homeostasis.

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“…Finally, among the nitrogen-containing group of phytochemicals, examples of potentially beneficial compounds in neurodegeneration/neurotoxicity here taken into account are sulforaphane (belonging to the glucosinolates group and found in cruciferous vegetables such as broccoli, cabbage, brussels sprouts, and cauliflower) [ 64 , 122 , 123 , 124 ] and spermine/spermidine (a polyamine found in soybean seeds) [ 68 , 125 , 126 , 127 ].…”

Section: An Overview Of Neuroprotective Phytochemical Classesmentioning

confidence: 99%

“…Besides phytochemical-protein interaction, the induction of autophagy fostering degradation of misfolded/aggregated proteins represents a key mechanism underlining the neuroprotective effects of phytochemicals. Caffeic acid, curcumin, dihydromyricetin, salvianolic acid, and spermine, through autophagy activation following mTOR inhibition or Beclin-1 recruitment, prevent α-syn aggregation and provide neuroprotection against α-syn-induced neurotoxicity in PD models [ 54 , 62 , 126 , 220 ]. The beneficial effects of these compounds are instead occluded by pharmacological autophagy inhibitors [ 54 , 62 , 126 , 220 ].…”

Section: Phytochemicals and Proteostasismentioning

confidence: 99%

“…Caffeic acid, curcumin, dihydromyricetin, salvianolic acid, and spermine, through autophagy activation following mTOR inhibition or Beclin-1 recruitment, prevent α-syn aggregation and provide neuroprotection against α-syn-induced neurotoxicity in PD models [ 54 , 62 , 126 , 220 ]. The beneficial effects of these compounds are instead occluded by pharmacological autophagy inhibitors [ 54 , 62 , 126 , 220 ]. Curcumin, while reducing the levels of oxidized proteins in PD models, also promotes proteasome activation, thus abolishing the inhibitory effect exerted by oxidative neurotoxicants on this degradative system [ 221 ].…”

Section: Phytochemicals and Proteostasismentioning

confidence: 99%

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Merging the Multi-Target Effects of Phytochemicals in Neurodegeneration: From Oxidative Stress to Protein Aggregation and Inflammation

et al. 2020

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Wide experimental evidence has been provided in the last decade concerning the neuroprotective effects of phytochemicals in a variety of neurodegenerative disorders. Generally, the neuroprotective effects of bioactive compounds belonging to different phytochemical classes are attributed to antioxidant, anti-aggregation, and anti-inflammatory activity along with the restoration of mitochondrial homeostasis and targeting alterations of cell-clearing systems. Far from being independent, these multi-target effects represent interconnected events that are commonly implicated in the pathogenesis of most neurodegenerative diseases, independently of etiology, nosography, and the specific misfolded proteins being involved. Nonetheless, the increasing amount of data applying to a variety of neurodegenerative disorders joined with the multiple effects exerted by the wide variety of plant-derived neuroprotective agents may rather confound the reader. The present review is an attempt to provide a general guideline about the most relevant mechanisms through which naturally occurring agents may counteract neurodegeneration. With such an aim, we focus on some popular phytochemical classes and bioactive compounds as representative examples to design a sort of main highway aimed at deciphering the most relevant protective mechanisms which make phytochemicals potentially useful in counteracting neurodegeneration. In this frame, we emphasize the potential role of the cell-clearing machinery as a kernel in the antioxidant, anti-aggregation, anti-inflammatory, and mitochondrial protecting effects of phytochemicals.

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Spermine protects alpha-synuclein expressing dopaminergic neurons from manganese-induced degeneration

Cited by 29 publications

References 71 publications

Spermidine and spermine delay brain aging by inducing autophagy in SAMP8 mice

Spermidine and spermine delay brain aging by inducing autophagy in SAMP8 mice

Resveratrol Improves Bnip3-Related Mitophagy and Attenuates High-Fat-Induced Endothelial Dysfunction

Merging the Multi-Target Effects of Phytochemicals in Neurodegeneration: From Oxidative Stress to Protein Aggregation and Inflammation

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