Dietary spermidine improves cognitive function

Schroeder, Sabrina; Hofer, Sebastian J.; Zimmermann, Andreas; Pechlaner, Raimund; Dammbrueck, Christopher; Pendl, Tobias; Marcello, G. Mark; Pogatschnigg, Viktoria; Bergmann, Martina; Müller, Melanie; Gschiel, Verena; Ristic, Selena; Tadić, Jelena; Iwata, Koichi; Richter, Gesa; Farzi, Aitak; Üçal, Muammer; Schäfer, Ute; Poglitsch, Michael; Royer, P; Mekis, Ronald; Agreiter, Marlene; Tölle, Regine C; Sótonyi, Péter; Willeit, Johann; Mairhofer, Barbara; Niederkofler, Helga; Pallhuber, Irmgard; Rungger, Gregorio; Tilg, Herbert; Defrancesco, Michaela; Marksteiner, Josef; Sinner, Frank; Magnes, Christoph; Pieber, Thomas R.; Holzer, Peter; Kroemer, Guido; Carmona-Gutiérrez, Didac; Scorrano, Luca; Dengjel, Jörn; Madl, Tobias; Sedej, Simon; Sigrist, Stephan J.; Rácz, Bence; Kiechl, Stefan; Eisenberg, Tobias; Madeo, Frank

doi:10.1016/j.celrep.2021.108985

Cited by 110 publications

(121 citation statements)

References 81 publications

Supporting

Mentioning

114

Contrasting

Unclassified

Order By: Relevance

“…In this work, we analyzed four aminosterols, squalamine (SQ), des-squalamine (desSQ), α-squalamine (αSQ), and trodusquemine (TRO), with slightly different physicochemical properties (Figure 1). The investigation of the addition of polyamine groups to a sterol moiety is particularly interesting following recent reports about the remarkable ability of polyamines to modulate cellular homeostasis (Schroeder et al, 2021;Liang et al, 2021). TRO contains a spermine moiety as its polyamine side chain, while SQ and its derivatives have a spermidine linked to the fused sterol ring.…”

Section: Resultsmentioning

confidence: 99%

Squalamine and Its Derivatives Modulate the Aggregation of Amyloid-β and α-Synuclein and Suppress the Toxicity of Their Oligomers

et al. 2021

View full text Add to dashboard Cite

The aberrant aggregation of proteins is a key molecular event in the development and progression of a wide range of neurodegenerative disorders. We have shown previously that squalamine and trodusquemine, two natural products in the aminosterol class, can modulate the aggregation of the amyloid-β peptide (Aβ) and of α-synuclein (αS), which are associated with Alzheimer’s and Parkinson’s diseases. In this work, we expand our previous analyses to two squalamine derivatives, des-squalamine and α-squalamine, obtaining further insights into the mechanism by which aminosterols modulate Aβ and αS aggregation. We then characterize the ability of these small molecules to alter the physicochemical properties of stabilized oligomeric species in vitro and to suppress the toxicity of these aggregates to varying degrees toward human neuroblastoma cells. We found that, despite the fact that these aminosterols exert opposing effects on Aβ and αS aggregation under the conditions that we tested, the modifications that they induced to the toxicity of oligomers were similar. Our results indicate that the suppression of toxicity is mediated by the displacement of toxic oligomeric species from cellular membranes by the aminosterols. This study, thus, provides evidence that aminosterols could be rationally optimized in drug discovery programs to target oligomer toxicity in Alzheimer’s and Parkinson’s diseases.

show abstract

Section: Resultsmentioning

confidence: 99%

Squalamine and Its Derivatives Modulate the Aggregation of Amyloid-β and α-Synuclein and Suppress the Toxicity of Their Oligomers

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Thus, dietary Spd-S is obviously able to boost hypusination levels in the aged mammalian brain. Notably, the mitochondrial status of mossy fiber synapses was also age-protected by Spd-S (Maglione et al, 2019), and Spd-S was found to protect cognitive performance in aging mice (De Risi et al, 2020) (see also accompanying paper in this issue of Cell Reports by Schroeder et al [2021], their Figure 2C). Our findings described here should thus be of relevance concerning the physiological and molecular basis for the mechanistic exploration and therapeutic usage of Spd-S effects.…”

Section: Cell Reportsmentioning

confidence: 96%

eIF5A hypusination, boosted by dietary spermidine, protects from premature brain aging and mitochondrial dysfunction

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Finally, SPD supplementation fails to prevent memory impairment in Atg7 −/− and Atg8a −/− Drosophila, suggesting autophagy is required for SPD-mediated protection from AMI. Furthermore, recently, Madeo's group showed that SPD supplementation improves cognitive performance in flies and aged mice, which appears to be due to the effects of SPD on enhancing mitochondrial function in neuronal tissue through autophagy and mitophagy [46]. Additionally, a large-scale food survey studies revealed that higher dietary SPD intake is correlated with a reduced risk for age-related cognitive impairment and decline in humans [46].…”

Section: Neuroprotective Effects Of Polyaminesmentioning

confidence: 99%

Polyamine Homeostasis in Development and Disease

Nakanishi

Cleveland

2021

Medical Sciences

View full text Add to dashboard Cite

Polycationic polyamines are present in nearly all living organisms and are essential for mammalian cell growth and survival, and for development. These positively charged molecules are involved in a variety of essential biological processes, yet their underlying mechanisms of action are not fully understood. Several studies have shown both beneficial and detrimental effects of polyamines on human health. In cancer, polyamine metabolism is frequently dysregulated, and elevated polyamines have been shown to promote tumor growth and progression, suggesting that targeting polyamines is an attractive strategy for therapeutic intervention. In contrast, polyamines have also been shown to play critical roles in lifespan, cardiac health and in the development and function of the brain. Accordingly, a detailed understanding of mechanisms that control polyamine homeostasis in human health and disease is needed to develop safe and effective strategies for polyamine-targeted therapy.

show abstract

Dietary spermidine improves cognitive function

Cited by 110 publications

References 81 publications

Squalamine and Its Derivatives Modulate the Aggregation of Amyloid-β and α-Synuclein and Suppress the Toxicity of Their Oligomers

Squalamine and Its Derivatives Modulate the Aggregation of Amyloid-β and α-Synuclein and Suppress the Toxicity of Their Oligomers

eIF5A hypusination, boosted by dietary spermidine, protects from premature brain aging and mitochondrial dysfunction

Polyamine Homeostasis in Development and Disease

Contact Info

Product

Resources

About