Autophagy and neurodegeneration

Frake, Rebecca A.; Ricketts, Thomas C.; Menzies, Fiona M.; Rubinsztein, David C.

doi:10.1172/jci73944

Cited by 289 publications

(266 citation statements)

References 153 publications

Supporting

Mentioning

251

Contrasting

Unclassified

Order By: Relevance

“…The length of the repeat expansion is directly related to the aggregation propensity of the ataxin3 protein and is inversely related to the age of onset of the disease. Protein aggregates are considered to be the cause for neuronal dysfunction and death, which is supported by several lines of evidence showing that aggregate prevention or increased (autophagic) clearance delays neuronal death and degeneration in multiple model systems (1)(2)(3)(4).…”

Section: Introductionmentioning

confidence: 92%

“…Pauline M Snijder, 1* Madina Baratashvili, 2* Nicola A Grzeschik, 2 Henri G D Leuvenink, 3 Lucas Kuijpers, 2 Sippie Huitema, 1 Onno Schaap, 2 Ben N G Giepmans, 4 Jeroen Kuipers, 4 Jan Lj Miljkovic, 5 Aleksandra Mitrovic, 6 Eelke M Bos, 1 Csaba Szabó, 7 Harm H Kampinga, 2 Pascale F Dijkers, 2 Wilfred F A den Dunnen, 1 Milos R Filipovic, 5 Harry van Goor, 1* and Ody C M Sibon 2*…”

Section: Overexpression Of Cystathionine γ-Lyase Suppresses Detrimentmentioning

confidence: 99%

See 1 more Smart Citation

Overexpression of Cystathionine γ-Lyase Suppresses Detrimental Effects of Spinocerebellar Ataxia Type 3

Snijder

Baratashvili

Grzeschik

et al. 2015

Mol Med

View full text Add to dashboard Cite

Spinocerebellar ataxia type 3 (SCA3) is a polyglutamine (polyQ) disorder caused by a CAG repeat expansion in the ataxin-3 (ATXN3) gene resulting in toxic protein aggregation. Inflammation and oxidative stress are considered secondary factors contributing to the progression of this neurodegenerative disease. There is no cure that halts or reverses the progressive neurodegeneration of SCA3. Here we show that overexpression of cystathionine γ-lyase, a central enzyme in cysteine metabolism, is protective in a Drosophila model for SCA3. SCA3 flies show eye degeneration, increased oxidative stress, insoluble protein aggregates, reduced levels of protein persulfidation and increased activation of the innate immune response. Overexpression of Drosophila cystathionine γ-lyase restores protein persulfidation, decreases oxidative stress, dampens the immune response and improves SCA3-associated tissue degeneration. Levels of insoluble protein aggregates are not altered; therefore, the data implicate a modifying role of cystathionine γ-lyase in ameliorating the downstream consequence of protein aggregation leading to protection against SCA3-induced tissue degeneration. The cystathionine γ-lyase expression is decreased in affected brain tissue of SCA3 patients, suggesting that enhancers of cystathionine γ-lyase expression or activity are attractive candidates for future therapies.

show abstract

Section: Introductionmentioning

confidence: 92%

Section: Overexpression Of Cystathionine γ-Lyase Suppresses Detrimentmentioning

confidence: 99%

Overexpression of Cystathionine γ-Lyase Suppresses Detrimental Effects of Spinocerebellar Ataxia Type 3

Snijder

Baratashvili

Grzeschik

et al. 2015

Mol Med

View full text Add to dashboard Cite

show abstract

“…Autophagy is a eukaryotic intracellular pathway that carries out key aspects of cytoplasmic homeostasis (Mizushima et al, 2011;Frake et al, 2015;Kroemer, 2015) in addition to its independent nutritional and metabolic roles (Rabinowitz and White, 2010;Kenific and Debnath, 2015). The principal aspects of how the core autophagy machinery operates have been defined and are conserved form yeast to humans (Mizushima et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

TRIM-mediated precision autophagy targets cytoplasmic regulators of innate immunity

Kimura¹,

Jain²,

Choi³

et al. 2015

J Exp Med

View full text Add to dashboard Cite

“…Many of these anti-aging properties have been causally linked to the capacity of spermidine to ensure proteostasis through the stimulation of cytoprotective macroautophagy [15–17]. Age-associated conditions including cancer, neurodegeneration and cardiovascular diseases are directly connected to the intracellular accumulation of toxic debris, and its removal by autophagy constitutes a well-documented avenue for protection against age and disease [18–20]. …”

mentioning

confidence: 99%

Spermidine: a physiological autophagy inducer acting as an anti-aging vitamin in humans?

et al. 2018

View full text Add to dashboard Cite

Spermidine is a natural polyamine that stimulates cytoprotective macroautophagy/autophagy. External supplementation of spermidine extends lifespan and health span across species, including in yeast, nematodes, flies and mice. In humans, spermidine levels decline with aging, and a possible connection between reduced endogenous spermidine concentrations and age-related deterioration has been suggested. Recent epidemiological data support this notion, showing that an increased uptake of this polyamine with spermidine-rich food diminishes overall mortality associated with cardiovascular diseases and cancer. Here, we discuss nutritional and other possible routes to counteract the age-mediated decline of spermidine levels.

show abstract

Autophagy and neurodegeneration

Cited by 289 publications

References 153 publications

Overexpression of Cystathionine γ-Lyase Suppresses Detrimental Effects of Spinocerebellar Ataxia Type 3

Overexpression of Cystathionine γ-Lyase Suppresses Detrimental Effects of Spinocerebellar Ataxia Type 3

TRIM-mediated precision autophagy targets cytoplasmic regulators of innate immunity

Spermidine: a physiological autophagy inducer acting as an anti-aging vitamin in humans?

Contact Info

Product

Resources

About