2019
DOI: 10.3389/fendo.2018.00778
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Chaperone Mediated Autophagy in the Crosstalk of Neurodegenerative Diseases and Metabolic Disorders

Abstract: Chaperone Mediated Autophagy (CMA) is a lysosomal-dependent protein degradation pathway. At least 30% of cytosolic proteins can be degraded by this process. The two major protein players of CMA are LAMP-2A and HSC70. While LAMP-2A works as a receptor for protein substrates at the lysosomal membrane, HSC70 specifically binds protein targets and takes them for CMA degradation. Because of the broad spectrum of proteins able to be degraded by CMA, this pathway has been involved in physiological and pathological pr… Show more

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Cited by 79 publications
(64 citation statements)
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“…CMA targets~35% of soluble cytosolic proteins, which harbor a KFERQ (composed of sequence of amino acids includes lysine (K), phenylalanine (F), glutamic acid (E), arginine (R) and glutamine (Q)) consensus motif, for lysosomal degradation [215]. Cytosolic chaperones, heat-shock cognate protein of 70 kDa (hsc70) and heat shock protein 90 (Hsp90) recognize the KFERQ motif and deliver targeted proteins to the lysosomal surface for binding to lysosome-associated membrane protein-2A (LAMP-2A) [217,218]. Upon binding to LAMP-2A, the substrate protein is unfolded, translocated and rapidly degraded within the lysosomal lumen.…”
Section: Chaperone-mediated Autophagy (Cma)mentioning
confidence: 99%
“…CMA targets~35% of soluble cytosolic proteins, which harbor a KFERQ (composed of sequence of amino acids includes lysine (K), phenylalanine (F), glutamic acid (E), arginine (R) and glutamine (Q)) consensus motif, for lysosomal degradation [215]. Cytosolic chaperones, heat-shock cognate protein of 70 kDa (hsc70) and heat shock protein 90 (Hsp90) recognize the KFERQ motif and deliver targeted proteins to the lysosomal surface for binding to lysosome-associated membrane protein-2A (LAMP-2A) [217,218]. Upon binding to LAMP-2A, the substrate protein is unfolded, translocated and rapidly degraded within the lysosomal lumen.…”
Section: Chaperone-mediated Autophagy (Cma)mentioning
confidence: 99%
“…Instead, recent data suggest that CMA may play a role in NDs, including ALS (Ormeño et al, 2020 ). Indeed, CMA is essential in Parkinson’s disease where its dysregulation modifies the onset or progression of the disease (Arias and Cuervo, 2011 ; Cuervo, 2011 ; Alfaro et al, 2018 ; Kaushik and Cuervo, 2018 ). Alpha-synuclein protein, leucine-rich repeat kinase 2 (LRRK2), Parkinson disease protein 7 (PARK7), and DJ-1, as well as myocyte-specific enhancer factor 2D protein (MEF2D), which are dysregulated or mutated in Parkinson’s disease, are CMA substrates (Vogiatzi et al, 2008 ; Yang et al, 2009 ; Arias and Cuervo, 2011 ; Cuervo, 2011 ; Orenstein et al, 2013 ; Murphy et al, 2015 ; Alfaro et al, 2018 ; Kaushik and Cuervo, 2018 ).…”
Section: How the Protein Quality Control System Protects Against Misfmentioning
confidence: 99%
“…Indeed, CMA is essential in Parkinson’s disease where its dysregulation modifies the onset or progression of the disease (Arias and Cuervo, 2011 ; Cuervo, 2011 ; Alfaro et al, 2018 ; Kaushik and Cuervo, 2018 ). Alpha-synuclein protein, leucine-rich repeat kinase 2 (LRRK2), Parkinson disease protein 7 (PARK7), and DJ-1, as well as myocyte-specific enhancer factor 2D protein (MEF2D), which are dysregulated or mutated in Parkinson’s disease, are CMA substrates (Vogiatzi et al, 2008 ; Yang et al, 2009 ; Arias and Cuervo, 2011 ; Cuervo, 2011 ; Orenstein et al, 2013 ; Murphy et al, 2015 ; Alfaro et al, 2018 ; Kaushik and Cuervo, 2018 ). Alzheimer’s disease is also associated with CMA since the beta-amyloid peptide (Aβ), the microtubule-associated protein Tau or the Regulator of calcineurin 1 (RCAN1) are involved in Alzheimer’s disease and are dysregulated when CMA is altered (Liu et al, 2009 ; Wang et al, 2009 , 2010 ; Park et al, 2016 ).…”
Section: How the Protein Quality Control System Protects Against Misfmentioning
confidence: 99%
“…Thus, mTORC2 and macroautophagy seemed to be impaired, whereas lysosomal/endosomal processes were activated [51,52]. Chaperone-mediated autophagy (CMA) involves HSP70, LAMP2 and lysosomes to regulate cell metabolism, in ammation and the cell cycle in response to stress [28,53,54]. We found HSP70 family proteins upregulated in A673 cells, indicating CMA after AUY-VE treatment.…”
Section: Discussionmentioning
confidence: 84%