The effect of spermidine on memory performance in older adults at risk for dementia: A randomized controlled trial

Wirth, Miranka; Benson, Gloria; Schwarz, Claudia; Köbe, Theresa; Grittner, Ulrike; Schmitz, Dietmar; Sigrist, Stephan J.; Bohlken, Jens; Stekovic, Slaven; Madeo, Frank; Flöel, Agnes

doi:10.1016/j.cortex.2018.09.014

Cited by 114 publications

(103 citation statements)

References 35 publications

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“…clinicaltrials.gov identifier: NCT02755246) and suggests good tolerability and safety of the compound (Schwarz et al, 2018). Moreover, a small pilot trial has already revealed the beneficial effects of spermidine supplementation in elderly people with subjective cognitive decline (Wirth et al, 2018). Hydroxycitric Acid and Other AcCoA-Depleting Agents Hydroxycitric acid (HCA) acts as a competitive low-affinity inhibitor of ATP citrate lyase (ACLY), which generates cytosolic AcCoA and thus represents an AcCoA-depleting CRM.…”

Section: Resveratrol and Other Sirt1 Activatorsmentioning

confidence: 99%

Caloric Restriction Mimetics against Age-Associated Disease: Targets, Mechanisms, and Therapeutic Potential

et al. 2019

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Section: Resveratrol and Other Sirt1 Activatorsmentioning

confidence: 99%

Caloric Restriction Mimetics against Age-Associated Disease: Targets, Mechanisms, and Therapeutic Potential

et al. 2019

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“…by blocking endosomal acidification ( 32 ), which is important for SARS-CoV-2 entry ( 6 ). We further used our in vitro model to explore the possibility of prophylactic treatment with spermidine and niclosamide, which are well-tolerated, clinically applied ( 33 ) or FDA-approved ( 34 ) compounds, respectively. To assess the efficacy of pretreatment, VeroFM cells were preincubated with spermidine (100 μM) or niclosamide (5 μM) for 24 hours.…”

Section: Fig1mentioning

confidence: 99%

Analysis of SARS-CoV-2-controlled autophagy reveals spermidine, MK-2206, and niclosamide as putative antiviral therapeutics

Gassen

Papies

Bajaj

et al. 2020

Preprint

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21Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses an acute threat to public health 22 and the world economy, especially because no approved specific drugs or vaccines are available. 23Pharmacological modulation of metabolism-dependent cellular pathways such as autophagy reduced 24 propagation of highly pathogenic Middle East respiratory syndrome (MERS)-CoV. 25Here we show that SARS-CoV-2 infection limits autophagy by interfering with multiple metabolic 26 pathways and that compound-driven interventions aimed at autophagy induction reduce SARS-CoV-2 27 propagation in vitro. In-depth analyses of autophagy signaling and metabolomics indicate that SARS-28 CoV-2 reduces glycolysis and protein translation by limiting activation of AMP-protein activated kinase 29 (AMPK) and mammalian target of rapamycin complex 1 (mTORC1). Infection also downregulates 30 autophagy-inducing spermidine, and facilitates AKT1/SKP2-dependent degradation of autophagy-31 initiating Beclin-1 (BECN1). Targeting of these pathways by exogenous administration of spermidine, 32AKT inhibitor MK-2206, and the Beclin-1 stabilizing, antihelminthic drug niclosamide inhibited SARS- 33CoV-2 propagation by 85, 88, and >99%, respectively. In sum, SARS-CoV-2 infection causally diminishes 34 autophagy. A clinically approved and well-tolerated autophagy-inducing compound shows potential 35 for evaluation as a treatment against SARS-CoV-2. 36 37 38 (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.The copyright holder for this preprint this version posted April 15, 2020. . https://doi.org/10.1101 3 The current pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses an 39 imminent threat to global health. As of 15 April 2020, 1,878,489 individuals were infected in >200 40 countries, with >119,000 fatalities (1). SARS-CoV-2 infections cause CoV-associated disease 19 (COVID-41 19), which can lead to severe atypical pneumonia in humans (2). Currently, there are no approved 42 therapeutics or vaccines available. The development and licensing of new FDA-approved drugs takes 43 years, which is problematic given the urgent need for effective therapies against novel, rapidly 44 emergent diseases like COVID-19. Antiviral drug screenings are commonly based on testing FDA-45 approved compound libraries against cellular and viral components (3). However, these undirected 46 approaches lack functional insights into how the drugs affect virus propagation. Risk evaluations for 47 drug repurposing and development of new therapeutics would benefit from rational drug design 48 founded on known SARS-CoV-2-host interactions. 49 Compound-based targeting of cellular proteins that are essential for the virus life cycle has led to the 50 discovery of broadly reactive drugs against a range of CoVs (3-6). As virus propagation strongly 51 depends on energy and catabolic substrates of host cells, drug target identification should consider 52 the metabolism of infected cells (3)....

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“…spermidinreichen Weizenkeimextrakts. Das Erinnerungsvermögen (getestet über die Fähigkeit, zuvor gesehene Bilder genau wiederzuerkennen -ein klassischer Gedächtnistest) konnte so durch die Gabe von Spermidin verbessert werden [10].…”

Section: Experimentelle Untersuchungenunclassified

Spermidin als Demenzprotektor

Madeo¹,

Eisenberg²

2020

Zeitschrift für Komplementärmedizin

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SummarySpermidin ist eine natürliche im Organismus vorkommendeSubstanz des Aminosäurestoffwechsels. In Untersuchungenkonnte eine Aktivierung der Autophagiedurch Spermidin gezeigt werden. Dieser zelluläre Recyclingprozesswird v.a. durch Fasten ausgelöst und hatbelegte gesundheitsfördernde Wirkungen.Experimentelle und klinische Studien geben vielversprechendeHinweise für einen möglichen Einsatz von Spermidinzur Demenzprävention. Eine klinische Studiekonnte eine Korrelation des Spermidinspiegels mit derkognitiven Leistungsfähigkeit zeigen. Eine weitere Untersuchungdeutet auf eine verbesserte Gehirngesundheitbei Spermidinaufnahme mit der Nahrung hin.Weitere Untersuchungen sind notwendig, um das Potenzialdieser körpereigenen Substanz insbesondere zurProtektion von Demenzerkrankungen zu erhärten.

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The effect of spermidine on memory performance in older adults at risk for dementia: A randomized controlled trial

Cited by 114 publications

References 35 publications

Caloric Restriction Mimetics against Age-Associated Disease: Targets, Mechanisms, and Therapeutic Potential

Caloric Restriction Mimetics against Age-Associated Disease: Targets, Mechanisms, and Therapeutic Potential

Analysis of SARS-CoV-2-controlled autophagy reveals spermidine, MK-2206, and niclosamide as putative antiviral therapeutics

Spermidin als Demenzprotektor

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