Autophagy in synaptic development, function, and pathology

Shen, Dan-Na; Zhang, Lihui; Wei, Er-Qing; Yang, Yi

doi:10.1007/s12264-015-1536-6

Cited by 58 publications

(50 citation statements)

References 94 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Additionally, within individual patients, there is evidence of local hyperconnectivity and long-range hypoconnectivity (Kana et al, 2014; Maximo et al, 2013; Moseley et al, 2015). Synaptic remodeling depends on mTOR-regulated autophagy (Shehata and Inokuchi, 2014; Shehata et al, 2012; Shen et al, 2015; Shen and Ganetzky, 2009; Tang et al, 2014). Thus, insufficient autophagy results in over connection and excessive results in over-pruning.…”

Section: : Discussionmentioning

confidence: 99%

“…Autophagy remodels neurons and tightly regulates cellular energy based on available nutrients. The interplay between these two systems fine-tunes neuronal development through dendrite formation and elimination and maintains neuronal functions, such as long-term potentiation and long-term depression (Shen et al, 2015). A direction for pharmacological intervention is the development of separate inhibitors for the two systems, which is difficult because the two systems have similar upstream signals (Shen et al, 2015).…”

Section: : Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Endosomal system genetics and autism spectrum disorders: A literature review

Patak

Zhang-James

Faraone

2016

Neuroscience & Biobehavioral Reviews

View full text Add to dashboard Cite

Autism spectrum disorders (ASDs) are a group of debilitating neurodevelopmental disorders thought to have genetic etiology, due to their high heritability. The endosomal system has become increasingly implicated in ASD pathophysiology. In an attempt to summarize the association between endosomal system genes and ASDs we performed a systematic review of the literature. We searched PubMed for relevant articles. Simons Foundation Autism Research Initiative (SFARI) gene database was used to exclude articles regarding genes with less than minimal evidence for association with ASDs. Our search retained 55 articles reviewed in two categories: genes that regulate and genes that are regulated by the endosomal system. Our review shows that the endosomal system is a novel pathway implicated in ASDs as well as other neuropsychiatric disorders. It plays a central role in aspects of cellular physiology on which neurons and glial cells are particularly reliant, due to their unique metabolic and functional demands. The system shows potential for biomarkers and pharmacological intervention and thus more research into this pathway is warranted.

show abstract

Section: : Discussionmentioning

confidence: 99%

Section: : Discussionmentioning

confidence: 99%

Endosomal system genetics and autism spectrum disorders: A literature review

Patak

Zhang-James

Faraone

2016

Neuroscience & Biobehavioral Reviews

View full text Add to dashboard Cite

show abstract

“…Autophagy inhibition induced retinal gliosis in these mice. In addition, autophagosome accumulation in the inner nuclear and outer plexiform layers concurs with the presence of activated microglia [75,76], suggesting that autophagy is crucial in protecting the retina against inflammation.…”

Section: The Link Between Autophagy and Inflammasome In The Retinamentioning

confidence: 94%

Autophagy: A Role in the Apoptosis, Survival, Inflammation, and Development of the Retina

Lin

2018

Ophthalmic Res

View full text Add to dashboard Cite

Autophagy is a lysosomal degradation process that maintains cellular homeostasis by removing dysfunctional organelles and unfolded proteins. Increasing evidence has shown that autophagy proteins are involved in retinal physiology and pathology and that defective autophagy contributes to retinal degeneration. In retinal diseases, autophagy plays a dual role: promoting retinal cell survival and death. Autophagy at a normal level helps retinal cells defend themselves against harmful stress; however, excessive autophagy results in retinal deterioration. Both synergistic and antagonistic roles of autophagy and apoptosis in the retina have been reported in the literature. In this review, we summarize the roles of autophagy in the development of the retina and retinal diseases. This review highlights the importance of autophagy in retinal diseases, and targeting autophagy may provide a new therapeutic approach for retinal diseases.

show abstract

“…In this special issue, "Autophagy in Neural Function [15,[17][18][19][20][21][22][23][24][25][26][27][28] .…”

mentioning

confidence: 99%

“…Selective autophagy is generally believed to be beneficial to neuronal development and functions [17][18][19] .…”

mentioning

confidence: 99%

Selective role of autophagy in neuronal function and neurodegenerative diseases

Rui

2015

Neurosci. Bull.

View full text Add to dashboard Cite

·Editorial·Proteostasis is critical for neuronal maintenance and survival, and its imbalance leads to neurodegeneration with the hallmark of protein misfolding and aggregation [1] .Macroautophagy becomes a major route for the clearance of protein aggregates that are normally poor substrates for the proteasome, the other protein quality-control machinery [2] . As a fl ux process, macroautophagy (hereafter referred to as autophagy) involves the formation of the autophagosome, a double-membrane vesicle for engulfi ng unwanted cellular components such as protein aggregates, and the fusion of autophagosomes with lysosomes that contain many potent proteases for fi nal degradation [3] .In the past decades, the mechanism of autophagy has been intensively studied under starvation conditions. Autophagy is a hierarchical process involving the activation of ULK1, the initiating kinase, and many downstream events such as Beclin 1 complex activation and LC3 lipidation [3] . It has been well established that, during amino-acid starvation, mTOR, the master nutrient sensor, dissociates from and in turn activates ULK1 kinase [4] .Interestingly, upon energy starvation such as glucose depletion, the main energy sensor AMPK activates ULK1 through antagonizing mTOR-mediated ULK1 inhibitory phosphorylation [5] . It is generally believed that starvation induces non-selective autophagy that targets non-essential cellular components for degradation to provide building blocks for cellular survival in unfavorable conditions.In comparison with the well-characterized starvationinduced nonselective autophagy, the molecular mechanism of selective autophagy is largely unknown [6] . Selective autophagy is a comprehensive term that can be classifi ed into many different types such as aggrephagy, mitophagy, and lipophagy [7] . In particular, aggrephagy plays an important role in neuronal survival, as neurons are nondividing cells and cannot overcome cellular toxicity induced by protein aggregates through dilution effects. Therefore, aggrephagy becomes essential for neurons to preserve proteostasis. However, the underlying mechanism is yet to be uncovered. Recently, Huntingtin, the Huntington's disease gene product, was identifi ed as a scaffold protein for selective autophagy including aggrephagy, mitophagy, and lipophagy in mammalian cells, paving the way for further investigation in this emerging young field [8] . In addition, cargo receptor proteins such as p62 and NBR1 bring cargos to autophagosomes by interacting with the autophagosomal protein LC3 [9] . As both p62 and NBR1 contain ubiquitin-binding domains, the cargos modifi ed by lineage-specific ubiquitin play an important role in cargo recognition in selective autophagy. For instance, ubiquitin K63-modified substrates preferentially bind to p62 for autophagic degradation [10] .Selective autophagy has been linked to a variety of human diseases including but not limited to neurodegeneration and cancer [11] . For example, tau protein, implicated in Alzheimer's disease (AD), was shown to be ...

show abstract

Autophagy in synaptic development, function, and pathology

Cited by 58 publications

References 94 publications

Endosomal system genetics and autism spectrum disorders: A literature review

Endosomal system genetics and autism spectrum disorders: A literature review

Autophagy: A Role in the Apoptosis, Survival, Inflammation, and Development of the Retina

Selective role of autophagy in neuronal function and neurodegenerative diseases

Contact Info

Product

Resources

About