Biological Functions of Autophagy Genes: A Disease Perspective

Cell, Journal Year: 2019, Volume and Issue: 176(1-2), P. 11 - 42

Published: Jan. 1, 2019

Language: Английский

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An Autophagic Flux Probe that Releases an Internal Control

Molecular Cell, Journal Year: 2016, Volume and Issue: 64(4), P. 835 - 849

Published: Nov. 1, 2016

Language: Английский

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mTORC1 as the main gateway to autophagy

Essays in Biochemistry, Journal Year: 2017, Volume and Issue: 61(6), P. 565 - 584

Published: Dec. 12, 2017

Cells and organisms must coordinate their metabolic activity with changes in environment to ensure growth only when conditions are favourable. In order maintain cellular homoeostasis, a tight regulation between the synthesis degradation of components is essential. At epicentre nutrient sensing mechanistic target rapamycin complex 1 (mTORC1) which connects environmental cues, including factor availability as well stress, processes preserve homoeostasis. Under nutrient-rich mTORC1 promotes cell by stimulating biosynthetic pathways, proteins, lipids nucleotides, inhibiting catabolism through repression autophagic pathway. Its close signalling interplay energy sensor AMP-activated protein kinase (AMPK) dictates whether actively favours anabolic or catabolic processes. Underlining role coordination metabolism, its deregulation linked numerous human diseases ranging from disorders many cancers. Although can be modulated number different inputs, amino acids represent primordial cues that cannot compensated for any other stimuli. The understanding how signal has increased considerably last years; however this area research remains hot topic biomedical sciences. current ideas models proposed explain interrelationship acid sensing, autophagy subject present review.

Language: Английский

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mTOR and autophagy: A dynamic relationship governed by nutrients and energy

Seminars in Cell and Developmental Biology, Journal Year: 2014, Volume and Issue: 36, P. 121 - 129

Published: Aug. 23, 2014

Language: Английский

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The Four Faces of Autophagy: Implications for Cancer Therapy

Cancer Research, Journal Year: 2014, Volume and Issue: 74(3), P. 647 - 651

Published: Jan. 24, 2014

It is generally thought that autophagy has two primary and opposing functions in tumor cells response to stress induced by chemotherapy or radiation. One the cytoprotective function can theory be inhibited for therapeutic advantage sensitizing these treatment modalities. The other cytotoxic not observed with conventional modalities, but may promote cell killing either alone association apoptosis. In this commentary/review, we advance premise actually populated at least additional players. have termed nonprotective form of autophagy, where apparently carrying out autophagy-mediated degradative functions, inhibition does lead perceptible alterations drug radiation sensitivity. what now term cytostatic its activation results prolonged growth as well reduced clonogenic survival (loss reproductive capacity) absence actual loss viability through apoptosis necrosis; however, case cytototoxic protects from agent (drugs radiation) promotes autophagic response. view current clinical efforts exploit a strategy sensitization malignancies radiation, it critical recognize if and/or patient tumors, necessity function.

Language: Английский

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Autophagy in neurodegenerative diseases: pathogenesis and therapy

Brain Pathology, Journal Year: 2017, Volume and Issue: 28(1), P. 3 - 13

Published: July 13, 2017

The most prevalent pathological features of many neurodegenerative diseases are the aggregation misfolded proteins and loss certain neuronal populations. Autophagy, as major intracellular machinery for degrading aggregated damaged organelles, has been reported to be involved in occurrence changes disorders, including Alzheimer's disease, Parkinson's Huntington's disease amyotrophic lateral sclerosis. In this review, we summarize recent research progress topic provide a new perspective regarding autophagy regulation on pathogenesis diseases. Finally, discuss signaling molecules autophagy-related pathways therapeutic targets treatment these

Language: Английский

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Development of autophagy inducers in clinical medicine

Journal of Clinical Investigation, Journal Year: 2015, Volume and Issue: 125(1), P. 14 - 24

Published: Jan. 1, 2015

Defects in autophagy have been linked to a wide range of medical illnesses, including cancer as well infectious, neurodegenerative, inflammatory, and metabolic diseases. These observations led the hypothesis that inducers may prevent or treat certain clinical conditions. Lifestyle nutritional factors, such exercise caloric restriction, exert their known health benefits through pathway. Several currently available FDA-approved drugs shown enhance autophagy, this autophagy-enhancing action be repurposed for use novel indications. The development new are designed more selective function target organs is expected maximize while minimizing toxicity. This Review summarizes rationale current approaches developing medicine, factors considered defining disease targets therapy, potential treatment human health.

Language: Английский

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Autophagy and Microglia: Novel Partners in Neurodegeneration and Aging

International Journal of Molecular Sciences, Journal Year: 2017, Volume and Issue: 18(3), P. 598 - 598

Published: March 9, 2017

Autophagy is emerging as a core regulator of Central Nervous System (CNS) aging and neurodegeneration. In the brain, it has mostly been studied in neurons, where delivery toxic molecules organelles to lysosome by autophagy crucial for neuronal health survival. However, we propose that (dys)regulation microglia also affects innate immune functions such phagocytosis inflammation, which turn contribute pathophysiology neurodegenerative diseases. Herein, first describe basic concepts its regulation, discuss key aspects accurate monitoring at experimental level, summarize evidence linking impairment CNS senescence disease. We focus on acute, chronic, autoimmunity-mediated neurodegeneration, including ischemia/stroke, Alzheimer’s, Parkinson’s, Huntington’s diseases, multiple sclerosis. Next, actual potential impact microglial phagocytic inflammatory function. Thus, provide how may affect apoptotic cells, amyloid-β, synaptic material, myelin debris, regulate progression age-associated data regulation phenotype, known age-related brain dysfunction. Overall, update current knowledge microglia, highlight yet unexplored mechanisms whereby disease senescence.

Language: Английский

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Impaired Autophagy in the Lipid-Storage Disorder Niemann-Pick Type C1 Disease

Cell Reports, Journal Year: 2013, Volume and Issue: 5(5), P. 1302 - 1315

Published: Nov. 27, 2013

Autophagy dysfunction has been implicated in misfolded protein accumulation and cellular toxicity several diseases. Whether alterations autophagy also contribute to the pathology of lipid-storage disorders is not clear. Here, we show defective Niemann-Pick type C1 (NPC1) disease associated with cholesterol accumulation, where maturation autophagosomes impaired because amphisome formation caused by failure SNARE machinery, whereas lysosomal proteolytic function remains unaffected. Expression functional NPC1 rescues this defect. Inhibition causes accumulation. Compromised was seen disease-affected organs Npc1 mutant mice. Of potential therapeutic relevance that HP-β-cyclodextrin, which used for cholesterol-depletion treatment, impedes autophagy, stimulating restores its independent formation. Our data suggest a low dose HP-β-cyclodextrin does perturb coupled an inducer, may provide rational treatment strategy disease.

Language: Английский

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Diabetic retinopathy: loss of neuroretinal adaptation to the diabetic metabolic environment

Annals of the New York Academy of Sciences, Journal Year: 2014, Volume and Issue: 1311(1), P. 174 - 190

Published: March 27, 2014

Diabetic retinopathy (DR) impairs vision of patients with type 1 and 2 diabetes, associated vascular dysfunction occlusion, retinal edema, hemorrhage, inappropriate growth new blood vessels. The recent success biologic treatments targeting endothelial factor (VEGF) demonstrates that treating the aspects in later stages disease can preserve many patients. It would also be highly desirable to prevent onset or arrest its progression at a stage preceding appearance overt microvascular pathologies. DR is not necessarily linear but may follow series steps evolve over course multiple years. Abundant data suggest diabetes affects entire neurovascular unit retina, an early loss coupling, gradual neurodegeneration, gliosis, neuroinflammation occurring before observable In this article, we consider pathology from point view causes measurable dysfunctions complex integral network cell types produce maintain human vision.

Language: Английский

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