Parkin contributes to synaptic vesicle autophagy in Bassoon-deficient mice DOI Creative Commons

Sheila Hoffmann-Conaway,

Marisa M. Brockmann,

Katharina Schneider

et al.

eLife, Journal Year: 2020, Volume and Issue: 9

Published: May 4, 2020

Mechanisms regulating the turnover of synaptic vesicle (SV) proteins are not well understood. They thought to require poly-ubiquitination and degradation through proteasome, endo-lysosomal or autophagy-related pathways. Bassoon was shown negatively regulate presynaptic autophagy in part by scaffolding Atg5. Here, we show that increased knockout neurons depends on loss leads elevated levels ubiquitinated per se. Our data have a smaller SV pool size higher rate as indicated younger SV2. The E3 ligase Parkin is required for Bassoon-deficient knockdown normalized protein rescued impaired recycling. These indicate key regulator proteostasis autophagy-mediated clearance proteins.

Language: Английский

Spermidine in health and disease DOI Open Access
Frank Madeo, Tobias Eisenberg, Federico Pietrocola

et al.

Science, Journal Year: 2018, Volume and Issue: 359(6374)

Published: Jan. 25, 2018

Having your longevity and eating too Although caloric restriction has clear benefits for maximizing health span life span, it is sufficiently unpleasant that few humans stick to it. Madeo et al. review evidence increased intake of the polyamine spermidine appears reproduce many healthful effects restriction, they explain its cellular actions, which include enhancement autophagy protein deacetylation. Spermidine found in foods such as wheat germ, soybeans, nuts, some fruits vegetables produced by microbiota. Increased uptake protective against cancer, metabolic disease, heart neurodegeneration. Science , this issue p. eaan2788

Language: Английский

Citations

847

Autophagy as a promoter of longevity: insights from model organisms DOI
Malene Hansen, David C. Rubinsztein, David W. Walker

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2018, Volume and Issue: 19(9), P. 579 - 593

Published: July 13, 2018

Language: Английский

Citations

648

Higher spermidine intake is linked to lower mortality: a prospective population-based study DOI Creative Commons
Stefan Kiechl, Raimund Pechlaner, Peter Willeit

et al.

American Journal of Clinical Nutrition, Journal Year: 2018, Volume and Issue: 108(2), P. 371 - 380

Published: April 30, 2018

Language: Английский

Citations

197

Dietary spermidine improves cognitive function DOI Creative Commons

Sabrina Schroeder,

Sebastian J. Hofer, Andreas Zimmermann

et al.

Cell Reports, Journal Year: 2021, Volume and Issue: 35(2), P. 108985 - 108985

Published: April 1, 2021

Decreased cognitive performance is a hallmark of brain aging, but the underlying mechanisms and potential therapeutic avenues remain poorly understood. Recent studies have revealed health-protective lifespan-extending effects dietary spermidine, natural autophagy-promoting polyamine. Here, we show that spermidine passes blood-brain barrier in mice increases hippocampal eIF5A hypusination mitochondrial function. Spermidine feeding aged affects behavior homecage environment tasks, improves spatial learning, respiratory competence. In Drosophila aging model, boosts capacity, an effect requires autophagy regulator Atg7 mitophagy mediators Parkin Pink1. Neuron-specific Pink1 knockdown abolishes spermidine-induced improvement olfactory associative learning. This suggests maintenance autophagic function essential for enhanced cognition by feeding. Finally, large-scale prospective data linking higher intake with reduced risk impairment humans.

Language: Английский

Citations

158

Polyamines in Parkinson's Disease: Balancing Between Neurotoxicity and Neuroprotection DOI Creative Commons
Stephanie Vrijsen, Marine Houdou, Ana Cascalho

et al.

Annual Review of Biochemistry, Journal Year: 2023, Volume and Issue: 92(1), P. 435 - 464

Published: April 5, 2023

The polyamines putrescine, spermidine, and spermine are abundant polycations of vital importance in mammalian cells. Their cellular levels tightly regulated by degradation synthesis, as well uptake export. Here, we discuss the delicate balance between neuroprotective neurotoxic effects context Parkinson's disease (PD). Polyamine decline with aging altered patients PD, whereas recent mechanistic studies on ATP13A2 (PARK9) demonstrated a driving role disturbed polyamine homeostasis PD. Polyamines affect pathways PD pathogenesis, such α-synuclein aggregation, influence PD-related processes like autophagy, heavy metal toxicity, oxidative stress, neuroinflammation, lysosomal/mitochondrial dysfunction. We formulate outstanding research questions regarding their potential biomarkers, possible therapeutic strategies for targeting homeostasis.

Language: Английский

Citations

44

Neuronal Autophagy: Regulations and Implications in Health and Disease DOI Creative Commons

Caroline Liénard,

Alexandre Pintart,

Pascale Bomont

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(1), P. 103 - 103

Published: Jan. 4, 2024

Autophagy is a major degradative pathway that plays key role in sustaining cell homeostasis, integrity, and physiological functions. Macroautophagy, which ensures the clearance of cytoplasmic components engulfed double-membrane autophagosome fuses with lysosomes, orchestrated by complex cascade events. has particularly strong impact on nervous system, mutations core cause numerous neurological diseases. We first review regulation autophagy, from biogenesis to lysosomal degradation associated neurodevelopmental/neurodegenerative disorders. then describe how this process specifically regulated axon somatodendritic compartment it altered In particular, we present neuronal specificities spatial control biogenesis, close relationship maturation axonal transport, synaptic activity. Finally, discuss functions autophagy during development adulthood.

Language: Английский

Citations

20

A primary cilia–autophagy axis in hippocampal neurons is essential to maintain cognitive resilience DOI Creative Commons
Manon Rivagorda, David Romeo-Guitart,

Victoria Blanchet

et al.

Nature Aging, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 21, 2025

Language: Английский

Citations

4

Autophagy in the presynaptic compartment in health and disease DOI Creative Commons
V. A. Vijayan, Patrik Verstreken

The Journal of Cell Biology, Journal Year: 2017, Volume and Issue: 216(7), P. 1895 - 1906

Published: May 17, 2017

Synapses are functionally distinct neuronal compartments that critical for brain function, with synaptic dysfunction being an early pathological feature in aging and disease. Given the large number of proteins needed proliferation defective subsequent loss protein homeostasis may be a leading cause dysfunction. Autophagic mechanisms cellular digestion processes recycle components contribute to homeostasis. Autophagy is important within nervous system, but its function specific such as synapse has been unclear. Evidence from research on both autophagy suggests there links between two during requires regulate Exciting new work autophagy-modulating enriched at begun link synapses A better understanding these will help us harness potential therapeutic benefits combating age-related disorders system.

Language: Английский

Citations

169

Anti-senescence compounds: A potential nutraceutical approach to healthy aging DOI

Felicia Gurău,

Simone Baldoni, Francesco Prattichizzo

et al.

Ageing Research Reviews, Journal Year: 2018, Volume and Issue: 46, P. 14 - 31

Published: May 6, 2018

Language: Английский

Citations

153

The effect of spermidine on memory performance in older adults at risk for dementia: A randomized controlled trial DOI
Miranka Wirth, Gloria Benson, Claudia Schwarz

et al.

Cortex, Journal Year: 2018, Volume and Issue: 109, P. 181 - 188

Published: Oct. 4, 2018

Language: Английский

Citations

133