Chaperone-mediated autophagy and disease: Implications for cancer and neurodegeneration

Gómez‐Sintes, Raquel; Arias, Esperanza

doi:10.1016/j.mam.2021.101025

Cited by 20 publications

(15 citation statements)

References 162 publications

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“…Interestingly, CMA upregulation in microglial cells and astrocytes also prevents brain inflammation and toxicity, resulting in neurodegeneration [ 82 ]. CMA is needed by glial cells, which occurs in neurons to avoid accumulation of poorly processed proteins that cause severe brain damage [ 22 , 34 ]. Microglia can degrade IKKβ and reduces TNF-α expression levels through CMA in response to a specific stimulus [ 83 ].…”

Section: Possible Therapeutic Approaches Based On Cma Inhibition In P...mentioning

confidence: 99%

“…The aging process strongly influences CMA as LAMP-2A levels at the lysosomal membrane becomes less stable at later stages of life. Thus, during aging, a decreased CMA activity causes a lower quality control of proteins and the accumulation of defective proteins, promoting malignant transformation of cells [ 18 , 32 , 33 , 34 ].…”

Section: Introductionmentioning

confidence: 99%

“…While physiological CMA levels are needed for cell homeostasis and avoid malignant cell transformation by preventing DNA damage and increasing proteostasis [ 35 ], CMA activity becomes pro-oncogenic when dysregulated. Transformed cells abnormally upregulate CMA activity, which degrades different tumor cell survival- and proliferation-inhibitory proteins [ 32 , 34 , 36 ]. In addition, increased CMA is required to sustain the characteristic Warburg metabolism in tumor cells as it is essential to degrade the majority of glycolytic enzymes and, therefore, to induce anaerobic glycolysis needed for cancer progression [ 24 , 37 ].…”

Section: Introductionmentioning

confidence: 99%

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Chaperone-Mediated Autophagy in Pericytes: A Key Target for the Development of New Treatments against Glioblastoma Progression

Salinas

Valdor

2022

IJMS

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Glioblastoma (GB) cells physically interact with peritumoral pericytes (PCs) present in the brain microvasculature. These interactions facilitate tumor cells to aberrantly increase and benefit from chaperone-mediated autophagy (CMA) in the PC. GB-induced CMA leads to major changes in PC immunomodulatory phenotypes, which, in turn, support cancer progression. In this review, we focus on the consequences of the GB-induced up-regulation of CMA activity in PCs and evaluate how manipulation of this process could offer new strategies to fight glioblastoma, increasing the availability of treatments for this cancer that escapes conventional therapies. We finally discuss the use of modified PCs unable to increase CMA in response to GB as a cell therapy alternative to minimize undesired off-target effects associated with a generalized CMA inhibition.

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Section: Possible Therapeutic Approaches Based On Cma Inhibition In P...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Chaperone-Mediated Autophagy in Pericytes: A Key Target for the Development of New Treatments against Glioblastoma Progression

Salinas

Valdor

2022

IJMS

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“…Effective macroautophagy is often referred to as "cell cleansing", and, when of moderate intensity, and appropriately balanced by synthesis of new proteins and organelles-particularly mitochondria, produced in the complex process of "mitochondrial biogenesis"-it is generally thought to enhance health span [1][2][3][4]. (Henceforth, macroautophagy will be referred to simply as "autophagy"-albeit chaperone-mediated autophagy and microautophagy are distinct processes that also assist in protein disposal within autophagosomes [5,6].) Measures which are known to increase median and maximal lifespan in rodents typically are associated with increased autophagy.…”

Section: Boosting Autophagy For Health Protectionmentioning

confidence: 99%

Nutraceutical and Dietary Strategies for Up-Regulating Macroautophagy

McCarty

2022

IJMS

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Macroautophagy is a “cell cleansing” process that rids cells of protein aggregates and damaged organelles that may contribute to disease pathogenesis and the dysfunctions associated with aging. Measures which boost longevity and health span in rodents typically up-regulate macroautophagy, and it has often been suggested that safe strategies which can promote this process in humans may contribute to healthful aging. The kinase ULK1 serves as a trigger for autophagy initiation, and the transcription factors TFEB, FOXO1, ATF4 and CHOP promote expression of a number of proteins which mediate macroautophagy. Nutraceutical or dietary measures which stimulate AMPK, SIRT1, eIF5A, and that diminish the activities of AKT and mTORC1, can be expected to boost the activities of these pro-autophagic factors. The activity of AMPK can be stimulated with the phytochemical berberine. SIRT1 activation may be achieved with a range of agents, including ferulic acid, melatonin, urolithin A, N1-methylnicotinamide, nicotinamide riboside, and glucosamine; correction of ubiquinone deficiency may also be useful in this regard, as may dietary strategies such as time-restricted feeding or intermittent fasting. In the context of an age-related decrease in cellular polyamine levels, provision of exogenous spermidine can boost the hypusination reaction required for the appropriate post-translational modification of eIF5A. Low-protein plant-based diets could be expected to increase ATF4 and CHOP expression, while diminishing IGF-I-mediated activation of AKT and mTORC1. Hence, practical strategies for protecting health by up-regulating macroautophagy may be feasible.

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“…So, in physiological conditions, CMA activity has the capability of protecting cells by the preservation of cellular integrity—also against malignant transformation. However, once cellular damage reaches a limit where this pathway gets dysregulated, CMA is able to facilitate cells—and that includes now tumorigenic transformed cells, survival and growth—and so contributing to the tumor progression ( 5 , 6 ). Consequently, understanding the basis of this dual role for CMA between physiological/anti-oncogenic and physiopathological/pro-oncogenic becomes essential; and acquires even a higher level of relevance in the case of very aggressive tumors, as the one debated here: GBM.…”

mentioning

confidence: 99%