Impact of Chaperone-Mediated Autophagy in Brain Aging: Neurodegenerative Diseases and Glioblastoma

Auzmendi-Iriarte, Jaione; Matheu, Ander

doi:10.3389/fnagi.2020.630743

Cited by 23 publications

(35 citation statements)

References 190 publications

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“…For a protein to be selectively degraded via the CMA pathway, it needs to have the pentapeptide motif of KFERQ in its protein sequence [382]. CMA has been shown to participate in both physiological and pathological situations, including the cell cycle, maintaining hematopoietic stem-cell function, aging, neurodegenerative diseases, and cancers [383][384][385][386][387][388][389]. CMA is also regulated at different levels, from cell membrane proteins to chaperone proteins in the cytoplasm, through Lamp2a, Hsc70, GFAP, EF1α, and the mTORC2/PHLPP1/Akt signaling axis [390][391][392].…”

Section: Chaperone-mediated Autophagymentioning

confidence: 99%

Over Fifty Years of Life, Death, and Cannibalism: A Historical Recollection of Apoptosis and Autophagy

Izadi

Ali

Pourkarimi

2021

IJMS

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Research in biomedical sciences has changed dramatically over the past fifty years. There is no doubt that the discovery of apoptosis and autophagy as two highly synchronized and regulated mechanisms in cellular homeostasis are among the most important discoveries in these decades. Along with the advancement in molecular biology, identifying the genetic players in apoptosis and autophagy has shed light on our understanding of their function in physiological and pathological conditions. In this review, we first describe the history of key discoveries in apoptosis with a molecular insight and continue with apoptosis pathways and their regulation. We touch upon the role of apoptosis in human health and its malfunction in several diseases. We discuss the path to the morphological and molecular discovery of autophagy. Moreover, we dive deep into the precise regulation of autophagy and recent findings from basic research to clinical applications of autophagy modulation in human health and illnesses and the available therapies for many diseases caused by impaired autophagy. We conclude with the exciting crosstalk between apoptosis and autophagy, from the early discoveries to recent findings.

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Section: Chaperone-mediated Autophagymentioning

confidence: 99%

Over Fifty Years of Life, Death, and Cannibalism: A Historical Recollection of Apoptosis and Autophagy

Izadi

Ali

Pourkarimi

2021

IJMS

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“…Proteostasis is strongly associated with the recognition and removal of unwanted proteins to ensure protein quality control. Unwanted, damaged, misfolded, and aggregated proteins are mainly degraded by the ubiquitin–proteasome system (UPS) and the lysosome-dependent autophagic process [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…The timely degradation of specific proteins by CMA can regulate multiple cellular functions, such as glucose and lipid metabolism, DNA repair, and cellular reprograming [ 6 ]. Many studies have revealed that CMA dysfunction is related to the pathologies of various human diseases, such as cardiac diseases, liver diseases, cancer, and neurodegenerative diseases [ 4 , 6 , 13 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Chaperone-Mediated Autophagy in Neurodegenerative Diseases and Acute Neurological Insults in the Central Nervous System

Kanno

Handa

Murakami

et al. 2022

Cells

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Autophagy is an important function that mediates the degradation of intracellular proteins and organelles. Chaperone-mediated autophagy (CMA) degrades selected proteins and has a crucial role in cellular proteostasis under various physiological and pathological conditions. CMA dysfunction leads to the accumulation of toxic protein aggregates in the central nervous system (CNS) and is involved in the pathogenic process of neurodegenerative diseases, including Parkinson’s disease and Alzheimer’s disease. Previous studies have suggested that the activation of CMA to degrade aberrant proteins can provide a neuroprotective effect in the CNS. Recent studies have shown that CMA activity is upregulated in damaged neural tissue following acute neurological insults, such as cerebral infarction, traumatic brain injury, and spinal cord injury. It has been also suggested that various protein degradation mechanisms are important for removing toxic aberrant proteins associated with secondary damage after acute neurological insults in the CNS. Therefore, enhancing the CMA pathway may induce neuroprotective effects not only in neurogenerative diseases but also in acute neurological insults. We herein review current knowledge concerning the biological mechanisms involved in CMA and highlight the role of CMA in neurodegenerative diseases and acute neurological insults. We also discuss the possibility of developing CMA-targeted therapeutic strategies for effective treatments.

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“…It is primarily a degradative pathway characterized as a fast route by which damaged cytoplasmic materials (collectively named 'cargo') are delivered to the lysosomes for recycling. Autophagy can be categorized into 3 subtypes called, micro-autophagy, macro-autophagy, and chaperone-mediated autophagy (for more detailed insights into the different autophagic pathways see (8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

A Key Pathway to Cancer Resilience: The Role of Autophagy in Glioblastomas

et al. 2021

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There are no effective strategies for the successful treatment of glioblastomas (GBM). Current therapeutic modalities effectively target bulk tumor cells but leave behind marginal GBM cells that escape from the surgical margins and radiotherapy field, exhibiting high migratory phenotype and resistance to all available anti-glioma therapies. Drug resistance is mostly driven by tumor cell plasticity: a concept associated with reactivating transcriptional programs in response to adverse and dynamic conditions from the tumor microenvironment. Autophagy, or “self-eating”, pathway is an emerging target for cancer therapy and has been regarded as one of the key drivers of cell plasticity in response to energy demanding stress conditions. Many studies shed light on the importance of autophagy as an adaptive mechanism, protecting GBM cells from unfavorable conditions, while others recognize that autophagy can kill those cells by triggering a non-apoptotic cell death program, called ‘autophagy cell death’ (ACD). In this review, we carefully analyzed literature data and conclude that there is no clear evidence indicating the presence of ACD under pathophysiological settings in GBM disease. It seems to be exclusively induced by excessive (supra-physiological) stress signals, mostly from in vitro cell culture studies. Instead, pre-clinical and clinical data indicate that autophagy is an emblematic example of the ‘dark-side’ of a rescue pathway that contributes profoundly to a pro-tumoral adaptive response. From a standpoint of treating the real human disease, only combinatorial therapy targeting autophagy with cytotoxic drugs in the adjuvant setting for GBM patients, associated with the development of less toxic and more specific autophagy inhibitors, may inhibit adaptive response and enhance the sensibility of glioma cells to conventional therapies.

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Impact of Chaperone-Mediated Autophagy in Brain Aging: Neurodegenerative Diseases and Glioblastoma

Cited by 23 publications

References 190 publications

Over Fifty Years of Life, Death, and Cannibalism: A Historical Recollection of Apoptosis and Autophagy

Over Fifty Years of Life, Death, and Cannibalism: A Historical Recollection of Apoptosis and Autophagy

Chaperone-Mediated Autophagy in Neurodegenerative Diseases and Acute Neurological Insults in the Central Nervous System

A Key Pathway to Cancer Resilience: The Role of Autophagy in Glioblastomas

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