Is the Modulation of Autophagy the Future in the Treatment of Neurodegenerative Diseases?

González‐Polo, Rosa A.; Pizarro-Estrella, Elisa; Yakhine-Diop, Sokhna M. S.; Rodríguez-Arribas, Mario; Gómez‐Sánchez, Rubén; Pedro, José Manuel Bravo-San; Fuentes, José

doi:10.2174/1568026615666150610130645

Cited by 11 publications

(8 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…20,21 This concept has been borne out in numerous model systems, and dysfunctional autophagy has been implicated in neurodegenerative diseases such as Alzheimer and Huntington diseases. [22][23][24] In rod photoreceptors the light-/dark-induced translocation of phototransduction proteins is thought to regulate light sensitivity whereby the concentration of transducin and ARR/arrestin in the photoreceptor OS is the critical factor. In bright light the translocation of transducin from the OS reduces sensitivity and the movement of ARR/arrestin into the OS quenches rhodopsin activation.…”

Section: Discussionmentioning

confidence: 99%

Autophagy-mediated catabolism of visual transduction proteins prevents retinal degeneration

Yao

Feathers

et al. 2016

Autophagy

View full text Add to dashboard Cite

Autophagy is a lysosomal degradation pathway critical to preventing the accumulation of cytotoxic proteins. Deletion of the essential autophagy gene Atg5 from the rod photoreceptors of the retina (atg5 Drod mouse) results in the accumulation of the phototransduction protein transducin and the degeneration of these neurons. The purpose of this study is to test the hypothesis that autophagic degradation of visual transduction proteins prevents retinal degeneration. Targeted deletion of both Gnat1 (a gene encoding the a subunit of the heterotrimeric G-protein transducin) and Atg5 in the rod photoreceptors resulted in a significantly decreased rate of rod cell degeneration as compared to the atg5Drod mouse retina, and considerable preservation of photoreceptors. Supporting this we used a novel technique to immunoprecipitate green fluorescent protein (GFP)-tagged autophagosomes from the retinas of the GFP-LC3 mice and demonstrated that the visual transduction proteins transducin and ARR/ arrestin are associated with autophagosome-specific proteins. Altogether, this study shows that degradation of phototransduction proteins by autophagy is necessary to prevent retinal degeneration. In addition, we demonstrate a simple and easily reproducible immunoisolation technique for enrichment of autophagosomes from the GFP-LC3 mouse retina, providing a novel application to the study of autophagosome contents across different organs and specific cell types in vivo.

show abstract

Section: Discussionmentioning

confidence: 99%

Autophagy-mediated catabolism of visual transduction proteins prevents retinal degeneration

Yao

Feathers

et al. 2016

Autophagy

View full text Add to dashboard Cite

show abstract

“…Impairment of autophagy has been reported in PD models and might worsen the progression of PD pathogenesis [8]. Autophagy is a complex mechanism that is widely regulated through the mammalian target of rapamycin (mTOR) or AMPactivated protein kinase (AMPK) signaling [9] or acetylation [10]. The latter intervenes downstream of the mTOR pathway [10].…”

Section: Introductionmentioning

confidence: 99%

Impaired Mitophagy and Protein Acetylation Levels in Fibroblasts from Parkinson’s Disease Patients

et al. 2018

Self Cite

View full text Add to dashboard Cite

Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder. While most PD cases are idiopathic, the known genetic causes of PD are useful to understand common disease mechanisms. Recent data suggests that autophagy is regulated by protein acetylation mediated by histone acetyltransferase (HAT) and histone deacetylase (HDAC) activities. The changes in histone acetylation reported to be involved in PD pathogenesis have prompted this investigation of protein acetylation and HAT and HDAC activities in both idiopathic PD and G2019S leucine-rich repeat kinase 2 (LRRK2) cell cultures. Fibroblasts from PD patients (with or without the G2019S LRRK2 mutation) and control subjects were used to assess the different phenotypes between idiopathic and genetic PD. G2019S LRRK2 mutation displays increased mitophagy due to the activation of class III HDACs whereas idiopathic PD exhibits downregulation of clearance of defective mitochondria. This reduction of mitophagy is accompanied by more reactive oxygen species (ROS). In parallel, the acetylation protein levels of idiopathic and genetic individuals are different due to an upregulation in class I and II HDACs. Despite this upregulation, the total HDAC activity is decreased in idiopathic PD and the total HAT activity does not significantly vary. Mitophagy upregulation is beneficial for reducing the ROS-induced harm in genetic PD. The defective mitophagy in idiopathic PD is inherent to the decrease in class III HDACs. Thus, there is an imbalance between total HATs and HDACs activities in idiopathic PD, which increases cell death. The inhibition of HATs in idiopathic PD cells displays a cytoprotective effect.

show abstract

“…It has a key role in cell homeostasis, nutrient deprivation and consequently prevents pathogenesis related to its dysregulation. 21 Indeed, diseases such as cancer 22 and neurodegenerative disorders have been associated with autophagy impairment. Generally, autophagy is downregulated in neurodegenerative diseases; however, an upregulation has been reported in certain cases.…”

Section: Oleuropein Induces Autophagymentioning

confidence: 99%

“…Chaperone-mediated autophagy involves the Heat Shock Cognate 70 (Hsc70) chaperone in the selection of the KFERQ motif in proteins that will translocate into lysosomes. 21 , 24 Microautophagy is a nonselective degradation that is characterized by a sequestration of cytosolic components through an invagination of the lysosomal membrane. 24 Finally, macroautophagy, often called autophagy, collects the cytosolic cargoes into some double-membrane vesicles namely autophagosomes that will later fusion with lysosomes to constitute lately the autophagolysosomes/autolysosomes.…”

Section: Oleuropein Induces Autophagymentioning

confidence: 99%

Biological effects of olive oil phenolic compounds on mitochondria

Blanco-Benítez

Calderón-Fernández

Canales-Cortés

et al. 2022

Molecular & Cellular Oncology

View full text Add to dashboard Cite

Phenolic compounds derived from olive oil have beneficial health properties against cancer, neurodegenerative, and metabolic diseases. Therefore, there are discrepancies in their impact on mitochondrial function that result in changes in oxidative capacity, mitochondrial respiration, and energetic demands. This review focuses on the versatile role of oleuropein, a potent antioxidant that regulates the AMPK/SIRT1/mTOR pathway to modulate autophagy/mitophagy and maintain metabolic homeostasis.

show abstract

Is the Modulation of Autophagy the Future in the Treatment of Neurodegenerative Diseases?

Cited by 11 publications

References 0 publications

Autophagy-mediated catabolism of visual transduction proteins prevents retinal degeneration

Autophagy-mediated catabolism of visual transduction proteins prevents retinal degeneration

Impaired Mitophagy and Protein Acetylation Levels in Fibroblasts from Parkinson’s Disease Patients

Biological effects of olive oil phenolic compounds on mitochondria

Contact Info

Product

Resources

About