Atg5 and Ambra1 differentially modulate neurogenesis in neural stem cells

Vázquez, Patricia; Arroba, Ana I.; Cecconi, Francesco; Rosa, Enrique J. de la; Boya, Patricia; Pablo, Flora de

doi:10.4161/auto.8.2.18535

Cited by 158 publications

(124 citation statements)

References 45 publications

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“…With regards to the central nervous system, the clinical findings of callosal agenesis, cortical hypoplasia, and cerebellar malformation connect EPG5-dependent autophagy to central nervous system development. Regulators of neuronal autophagy, such as Ambra1 or Atg5, have been found to play a crucial role during early neuronal differentiation 36,37 and postnatal adaptation 38 by assuring that basal autophagy disposes cellular components and provides energy to enable the dynamic changes necessary in the developing brain.…”

Section: Autophagy In Pediatric Brain Diseasesmentioning

confidence: 99%

Emerging role of autophagy in pediatric neurodegenerative and neurometabolic diseases

et al. 2013

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Pediatric neurodegenerative diseases are a heterogeneous group of diseases that result from specific genetic and biochemical defects. In recent years, studies have revealed a wide spectrum of abnormal cellular functions that include impaired proteolysis, abnormal lipid trafficking, accumulation of lysosomal content, and mitochondrial dysfunction. Within neurons, elaborated degradation pathways such as the ubiquitin-proteasome system and the autophagy-lysosomal pathway are critical for maintaining homeostasis and normal cell function. Recent evidence suggests a pivotal role for autophagy in major adult and pediatric neurodegenerative diseases. We herein review genetic, pathological, and molecular evidence for the emerging link between autophagy dysfunction and lysosomal storage disorders such as Niemann-Pick type C, progressive myoclonic epilepsies such as Lafora disease, and leukodystrophies such as Alexander disease. We also discuss the recent discovery of genetically deranged autophagy in Vici syndrome, a multisystem disorder, and the implications for the role of autophagy in development and disease. Deciphering the exact mechanism by which autophagy contributes to disease pathology may open novel therapeutic avenues to treat neurodegeneration. To this end, an outlook on novel therapeutic approaches targeting autophagy concludes this review. P ediatric neurodegenerative diseases are a heterogeneous group of diseases that result from specific genetic and biochemical defects. Although the age of onset and the clinical course are variable, neurodegenerative disorders of childhood are characterized by progressive neurologic and cognitive dysfunction with loss of speech, vision, hearing, and motor skills, and a frequent association with seizures, feeding difficulties, and failure to thrive. The degenerative process can affect white and gray matter and spreads in a disease-specific manner. Current genetic and biochemical testing and neuroimaging can establish a diagnosis. The outcome for most diseases, however, is still poor, as therapeutic approaches are limited.Accumulation of proteins, polysaccharides, and lipids are common mechanisms shared by major adult-onset neurodegenerative diseases 1-3 and many neurodegenerative diseases of childhood. 4 These conditions are, therefore, often referred to as "storage diseases" or "proteinopathies. " Cells and postmitotic cells such as neurons, in particular, rely on effective cargo targeting, tagging, transportation, and degradation to maintain intracellular homeostasis under normal conditions and metabolic stress. Within this network, autophagy plays an indispensible role by eliminating misfolded and aggregated proteins, lipids, saccharides, and damaged organelles. Recent evidence suggests that autophagy is dysregulated in a number of pediatric neurodegenerative and metabolic diseases. AUTOPHAGY: AN OVERVIEWAutophagy describes intracellular pathways that converge into degradation of target material in lysosomes. 5 The route of cargo delivery to the lysosome distinguishes th...

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Section: Autophagy In Pediatric Brain Diseasesmentioning

confidence: 99%

Emerging role of autophagy in pediatric neurodegenerative and neurometabolic diseases

et al. 2013

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“…3 So far, numerous evidences about the autophagy function have mainly concentrated on nervous system, such as, the differentiation of neuroepithelial cells or the neurodegeneration and behavioral deficits by Atg7 conditional knockout in mouse neurons. 4,5 However, autophagy functions on other types of cells remain controversial and much less was known about the function of Atg7 on the development of embryos. It was reported that mice with targeted mutations Atg7 died within 1 day after birth, and the weight of the Atg7 KO mice was significantly lower than that of normal mice.…”

Section: Introductionmentioning

confidence: 99%

Autophagy functions on EMT in gastrulation of avian embryo

Wang

et al. 2014

Cell Cycle

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y These authors contributed equally to this work.Keywords: autophagy, Atg7, EMT and chick embryo, gastrulation Abbreviations: 3-MA, 3-Methyladenine; BF, bright-field; DAPI, 49-6-Diamidino-2-phenylindole; EB, embryoid bodies; E-Cad, E-cadherin; EMTs, epithelial-mesenchymal transitions; GFP, green fluorescent protein; HN, Hensen's node; MAPILC3(LC3), microtubule-associated protein 1 light chain 3; mTOR, mammalian target of rapamycin; N-Cad, N-cadherin; NT, neural tube; PBS, phosphate-buffered saline; PCD, Programmed cell death; PD, idiopathic Parkinson's Disease; PI3K, phosphoinositide-3-kinase; PPIA, peptidylprolyl isomerase A; PS, primitive streak; RAPA, Rapamycin; RT-PCR, reverse transcription PCR; shh, sonic hedgehog.Autophagy is important for cell renewing for its contribution to the degradation of bulk cytoplasm, long-lived proteins, and entire organelles and its role in embryonic development is largely unknown. In our study, we investigated the function of autophagy in gastrulation of the chick embryo using both in vivo and in vitro approaches, especially in the EMT process, and we found that autophagy gene Atg7 was expressed on the apical side of the ectoderm and endoderm. Over-expression of Atg7 could enhance the expression of Atg8 and the E-cadherin, the latter of which is a crucial marker of the EMT process. We also found that the disturbance of autophagy could retard the development of chick embryos in HH4 with shorter primitive steak than that in the control group, which is a newly formed structure during EMT process. So we assumed that autophagy could affect EMT process by adhesion molecule expression. Moreover, more molecules, such as slug, chordin, shh et., which were all involved in EMT process, were detected to address the mechanism of this phenomena. We established that the inhibition of autophagy could cause developmental delay by affecting EMT process in gastrulation of chick embryos.

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“…In contrast, upregulation of autophagy-genes has also been shown during neuronal differentiation in mouse embryonic olfactory bulb (Vazquez et al, 2012). Vazquez and collogues also demonstrated that chemical inhibition of autophagy pathway will block the nervous system development in this animal (Vazquez et al, 2012).…”

Section: Autophagy and Stem Cellsmentioning

confidence: 97%

“…Different groups have demonstrated that ATG7 knock down in murine HSCs resulted in decelerated HSCs self-renewal and negatively affected myeloproliferation Mortensen et al, 2011). In contrast, upregulation of autophagy-genes has also been shown during neuronal differentiation in mouse embryonic olfactory bulb (Vazquez et al, 2012). Vazquez and collogues also demonstrated that chemical inhibition of autophagy pathway will block the nervous system development in this animal (Vazquez et al, 2012).…”

Section: Autophagy and Stem Cellsmentioning

confidence: 98%

“…In this context, autophagy may negatively regulates cellular apoptosis and senescence and therefore positively affecting the reprogramming progress (Menendez et al, 2011). On the other hand, in some experimental systems, mitochondrial targeted autophagy (mitophagy) (Jangamreddy and Los, 2012) facilitates reprogramming via decreasing reactive oxygen species production (Fimia et al, 2007;Vazquez et al, 2012).…”

Section: Autophagy and Stem Cellsmentioning

confidence: 99%

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Reprogramming and Carcinogenesis—Parallels and Distinctions

Wasik

Grabarek

Pantovic

et al. 2014

International Review of Cell and Molecular Biology

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Abbreviations: CDK -Cyclin-Dependent Kinase; CSC -cancer stem cells; DSB -double strand breaks ; ECM -extracellular matrix; ES cell -embryonic stem cell; GFP -green fluorescent protein; GSK3 -glycogen synthase kinase-3; HN -Hemagglutininneuraminidase; iPS -induced pluripotent stem cells; MSFs -myocardial scar fibroblasts; RB -Retinoblastoma protein; RGD -arginine-glycine-aspartic acid; RISC -RNA-induced silencing complex; Shc -Src homology 2 domain-containing.

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Atg5 and Ambra1 differentially modulate neurogenesis in neural stem cells

Cited by 158 publications

References 45 publications

Emerging role of autophagy in pediatric neurodegenerative and neurometabolic diseases

Emerging role of autophagy in pediatric neurodegenerative and neurometabolic diseases

Autophagy functions on EMT in gastrulation of avian embryo

Reprogramming and Carcinogenesis—Parallels and Distinctions

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