Role of Chaperone-Mediated Autophagy in Ageing and Neurodegeneration

2015 ◽  
pp. 25-40
Author(s):  
J.V. Ferreira ◽  
P. Pereira ◽  
H. Girao
Keyword(s):  
Chaperone Mediated Autophagy

scholarly journals The Role of Chaperone-Mediated Autophagy in Hepatitis C Virus-Induced Pathogenesis

2021 ◽  
Vol 11 ◽  
Author(s):  
Chieko Matsui ◽  
Putu Yuliandari ◽  
Lin Deng ◽  
Takayuki Abe ◽  
Ikuo Shoji
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Degradation Process ◽  
Degradation Pathway ◽  
Hepatocyte Nuclear Factor ◽  
Selective Degradation ◽  
Substrate Protein ◽  
Hepatocyte Nuclear Factor 1Α ◽  
Chaperone Mediated Autophagy

Lysosome incorporate and degrade proteins in a process known as autophagy. There are three types of autophagy; macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA). Although autophagy is considered a nonselective degradation process, CMA is known as a selective degradation pathway. All proteins internalized in the lysosome via CMA contain a pentapeptide KFERQ-motif, also known as a CMA-targeting motif, which is necessary for selectivity. CMA directly delivers a substrate protein into the lysosome lumen using the cytosolic chaperone HSC70 and the lysosomal receptor LAMP-2A for degradation. Hepatitis C virus (HCV) NS5A protein interacts with hepatocyte-nuclear factor 1α (HNF-1α) together with HSC70 and promotes the lysosomal degradation of HNF-1α via CMA, resulting in HCV-induced pathogenesis. HCV NS5A promotes recruitment of HSC70 to the substrate protein HNF-1α. HCV NS5A plays a crucial role in HCV-induced CMA. Further investigations of HCV NS5A-interacting proteins containing CMA-targeting motifs may help to elucidate HCV-induced pathogenesis.

scholarly journals Chaperone-Mediated Autophagy and Mitochondrial Homeostasis in Parkinson’s Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-7
Author(s):  
Ruixin Yang ◽  
Guodong Gao ◽  
Zixu Mao ◽  
Qian Yang
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Lewy Bodies ◽  
Substantia Nigra Pars Compacta ◽  
Mitochondrial Homeostasis ◽  
New Findings ◽  
Novel Therapeutic Strategies ◽  
Chaperone Mediated Autophagy

Parkinson’s disease (PD), a complex neurodegenerative disorder, is pathologically characterized by the formation of Lewy bodies and loss of dopaminergic neurons in the substantia nigra pars compacta (SNc). Mitochondrial dysfunction is considered to be one of the most important causative mechanisms. In addition, dysfunction of chaperone-mediated autophagy (CMA), one of the lysosomal proteolytic pathways, has been shown to play an important role in the pathogenesis of PD. An exciting and important development is recent finding that CMA and mitochondrial quality control may be linked. This review summarizes the studies revealing the link between autophagy and mitochondrial function. Discussions are focused on the connections between CMA and mitochondrial failure and on the role of MEF2D, a neuronal survival factor, in mediating the regulation of mitochondria in the context of CMA. These new findings highlight the need to further explore the possibility of targeting the MEF2D-mitochondria-CMA network in both understanding the PD pathogenesis and developing novel therapeutic strategies.

scholarly journals The role of chaperone mediated autophagy in the central nervous system

2019 ◽  
Author(s):  
Δάφνη Αντωνίου
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
The Central Nervous System ◽  
Chaperone Mediated Autophagy

Τα κυτταρικά συστήματα αποικοδόμησης πρωτεϊνών επηρεάζουν ουσιαστικά τα σηματοδοτικά μονοπάτια και μοριακά δίκτυα που ρυθμίζουν την οργανογένεση. Παρ'όλο που η αποικοδόμηση πρωτεϊνών μέσω αυτοφαγίας έχει συσχετιστεί πολύ ισχυρά με τη λειτουργία του εγκεφάλου και σχετικές ασθένειες, η συμμετοχή αυτής στην ανάπτυξη του νευρικού συστήματος παραμένει ασαφής. Η Αυτοφαγία Διαμεσολαβούμενη απο Σαπερόνες, ένα από τα κύρια λυσοσωμικά μονοπάτια, έχει συνδεθεί άμεσα με νευροεκφυλιστικές ασθένειες και ασθένειες σχετικές με την ανάπτυξη του εγκεφάλου, παρ' όλ' αυτά δεν υπάρχει κάτι γνωστό σχετικά με το φυσιολογικό ρόλο αυτής στην ανάπτυξη του εγκεφάλου των θηλαστικών. Με αυτή την εργασία παρουσιάζουμε ένα καινοτόμο ρυθμιστικό ρόλο της Αυτοφαγίας Διαμεσολαβούμενης απο Σαπερόνες, κατά τη διαφοροποίηση των Νευρικών Βλαστικών κυττάρων (ΝΒΚ) κατά τη διάρκεια της ανάπτυξης. Συγκεκριμένα, παρουσιάζουμε πως αυτό το μονοπάτι αυτοφαγίας είναι σημαντικά ενεργό στα ΝΒΚ και πως η LAMP2A, η βασικότερη πρωτεΐνη του μονοπατιού, μαζί με την HSC70 (HSPA8), ένα επιπλέον κομβικό μόριο για αυτό το αυτοφαγικό μονοπάτι, εκφράζονται σημαντικά και στα ΝΒΚ και στο εμβρυονικό εγκέφαλο των τρωκτικών. Επιπλέον, η LAMP2A συσχετίζεται με την έναρξη της νευρογένεσης. Πιο σημαντικά ακόμα, παρατηρείται πως υπερέκφραση και αποσιώπηση της LAMP2A οδηγεί στην ενεργοποίηση της νευρογένεσης κατά την διαφοροποίηση των ΝΒΚ. Σχετικά με τον μηχανισμό, στην μελέτη αυτή παρουσιάζεται πως η LAMP2A επηρεάζει την κυτταρική διαφοροποίηση των ΝΒΚ παρεμβαίνοντας στο NOTCH1 σηματοδοτικό μονοπάτι. Η υπερέκφραση της LAMP2A καταστέλλει την έκφραση του NICD (του ενδοκυτταρικού τμήματος της NOTH1 πρωτεΐνης που λειτουργεί ως μεταγραφικός παράγοντας στον πυρήνα) όπως επίσης και την έκφραση των γονιδίων που επάγει το NICD, το HES5 και HES1. Επιπρόσθετα, το γνωστό και αναγνωρίσιμο μοτίβο των πρωτεϊνών-στόχων στην αμινοξική τους αλληλουχία( KFERQ-like motif) της Αυτοφαγίας Διαμεσολαβούμενης απο Σαπερόνες , αναγνωρίστηκε στο NICD και φαίνεται να καθορίζει την ενεργότητά του σχετικά με την μεταγραφή των γονιδίων-στόχων. Η ρύθμιση αυτή φαίνεται να συμβαίνει μέσω της αποικοδόμησης της πρωτεΐνης NICD από το μονοπάτι της Αυτοφαγίας . Εν κατακλείδι, τα δεδομένα που προκύπτουν από την παρούσα εργασία οδηγούν στο συμπέρασμα ενός νέου ουσιαστικού ρόλου της LAMP2A και της Αυτοφαγίας Διαμεσολαβούμενης απο Σαπερόνες στην ρύθμιση της νευρονικής μοίρας του κυττάρου μέσω στόχευσης του NICD, επομένως και της ενεργότητας του NOTCH1 σηματοδοτικού μονοπατιού.

Role of chaperone-mediated autophagy in COPD pathogenesis

2018 ◽  
Author(s):  
Yusuke Hosaka ◽  
Jun Araya ◽  
Kazuya Tsubouchi ◽  
Shunsuke Minagawa ◽  
Hiromichi Hara ◽  
...  
Keyword(s):  
Chaperone Mediated Autophagy

scholarly journals Disturbed Cholesterol Traffic but Normal Proteolytic Function in LAMP-1/LAMP-2 Double-deficient Fibroblasts

2004 ◽  
Vol 15 (7) ◽  
pp. 3132-3145 ◽  
Author(s):  
Eeva-Liisa Eskelinen ◽  
Christine Katrin Schmidt ◽  
Silja Neu ◽  
Marion Willenborg ◽  
Graciela Fuertes ◽  
...  
Keyword(s):  
Fibroblast Cell ◽  
Cholesterol Homeostasis ◽  
Receptor Expression ◽  
Autophagic Vacuoles ◽  
Lysosome Biogenesis ◽  
Degradation Rates ◽  
Percoll Gradients ◽  
Chaperone Mediated Autophagy ◽  
Fibroblast Cell Lines

Mice double deficient in LAMP-1 and -2 were generated. The embryos died between embryonic days 14.5 and 16.5. An accumulation of autophagic vacuoles was detected in many tissues including endothelial cells and Schwann cells. Fibroblast cell lines derived from the double-deficient embryos accumulated autophagic vacuoles and the autophagy protein LC3II after amino acid starvation. Lysosomal vesicles were larger and more peripherally distributed and showed a lower specific density in Percoll gradients in double deficient when compared with control cells. Lysosomal enzyme activities, cathepsin D processing and mannose-6-phosphate receptor expression levels were not affected by the deficiency of both LAMPs. Surprisingly, LAMP-1 and -2 deficiencies did not affect long-lived protein degradation rates, including proteolysis due to chaperone-mediated autophagy. The LAMP-1/2 double-deficient cells and, to a lesser extent, LAMP-2 single-deficient cells showed an accumulation of unesterified cholesterol in endo/lysosomal, rab7, and NPC1 positive compartments as well as reduced amounts of lipid droplets. The cholesterol accumulation in LAMP-1/2 double-deficient cells could be rescued by overexpression of murine LAMP-2a, but not by LAMP-1, highlighting the more prominent role of LAMP-2. Taken together these findings indicate partially overlapping functions for LAMP-1 and -2 in lysosome biogenesis, autophagy, and cholesterol homeostasis.

scholarly journals Forms, Crosstalks, and the Role of Phospholipid Biosynthesis in Autophagy

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Leanne Pereira ◽  
John Paul Girardi ◽  
Marica Bakovic
Keyword(s):  
Phospholipid Synthesis ◽  
Phospholipid Biosynthesis ◽  
Lysosomal Degradation ◽  
Specific Mechanism ◽  
Membrane Formation ◽  
Cytoplasmic Material ◽  
Specific Proteins ◽  
Chaperone Mediated Autophagy ◽  
Periods Of Stress

Autophagy is a highly conserved cellular process occurring during periods of stress to ensure a cell's survival by recycling cytosolic constituents and making products that can be used in energy generation and other essential processes. Three major forms of autophagy exist according to the specific mechanism through which cytoplasmic material is transported to a lysosome. Chaperone-mediated autophagy is a highly selective form of autophagy that delivers specific proteins for lysosomal degradation. Microautophagy is a less selective form of autophagy that occurs through lysosomal membrane invaginations, forming tubes and directly engulfing cytoplasm. Finally, macroautophagy involves formation of new membrane bilayers (autophagosomes) that engulf cytosolic material and deliver it to lysosomes. This review provides new insights on the crosstalks between different forms of autophagy and the significance of bilayer-forming phospholipid synthesis in autophagosomal membrane formation.

scholarly journals The Role of Autophagy in Immunity and Autoimmune Diseases / Uloga Autofagije U Imunskom Odgovoru I Autoimunskim Bolestima

2014 ◽  
Vol 15 (4) ◽  
pp. 223-229
Author(s):  
Bojana Simovic Markovic ◽  
Ljubica Vucicevic ◽  
Sanja Bojic ◽  
Vladislav Volarevic
Keyword(s):  
Autoimmune Diseases ◽  
Potential Role ◽  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Physiological Role ◽  
Immune Functions ◽  
Complex Relationships ◽  
Cellular Components ◽  
Chaperone Mediated Autophagy

ABSTRACT Autophagy is a catabolic mechanism in the cell that involves the degradation of unnecessary or dysfunctional cellular components by the lysosomal machinery. Recent studies have indicated that autophagy is a source of autoantigens, thus highlighting its potential role in the pathogenesis of autoimmunity. There are at least three different forms of autophagy: macroautophagy, microautophagy and chaperone-mediated autophagy (CMA). The physiological role of autophagy is to maintain cellular homeostasis by removing long-lived, damaged proteins and dysfunctional organelles and by providing energy. Aberrant autophagy may contribute to chronic inflammatory diseases and autoimmune diseases. An understanding of the complex relationships between autophagy and autophagy-related genes in each autoimmune disease creates the possibility of developing more specific and effective therapeutic strategies. Given the importance of autophagy in immune functions, this review article summarises current knowledge about the role of autophagy in the pathogenesis of autoimmune diseases.

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