A role of small heat shock protein B8 (HspB8) in the autophagic removal of misfolded proteins responsible for neurodegenerative diseases.

Abstract:

:Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of upper and lower motor neurons. As with other age-dependent neurodegenerative disorders, ALS is linked to the presence of misfolded proteins that may perturb several intracellular mechanisms and trigger neurotoxicity. Misfolded proteins aggregate intracellularly generating insoluble inclusions that are a key neuropathological hallmark of ALS. Proteins involved in the intracellular degradative systems, signaling pathways and the human TAR DNA-binding protein TDP-43 are major components of these inclusions. While their role and cytotoxicity are still largely debated, aggregates represent a powerful marker to follow protein misfolding in the neurodegenerative processes. Using in vitro and in vivo models of mutant SOD1 associated familial ALS (fALS), we and other groups demonstrated that protein misfolding perturbs one of the major intracellular degradative pathways, the ubiquitin proteasome system, giving rise to a vicious cycle that leads to the further deposit of insoluble proteins and finally to the formation of inclusions. The aberrant response to mutated SOD1 thus leads to the activation of the cascade of events ultimately responsible for cell death. Hence, our idea is that, by assisting protein folding, we might reduce protein aggregation, restore a fully functional proteasome activity and/or other cascades of events triggered by the mutant proteins responsible for motor neuron death in ALS. This could be obtained by stimulating mutant protein turnover, using an alternative degradative pathway that could clear mutant SOD1, namely autophagy.

journal_name

Autophagy

journal_title

Autophagy

authors

Crippa V,Carra S,Rusmini P,Sau D,Bolzoni E,Bendotti C,De Biasi S,Poletti A

doi

10.4161/auto.6.7.13042

subject

Has Abstract

pub_date

2010-10-01 00:00:00

pages

958-60

issue

7

eissn

1554-8627

issn

1554-8635

pii

13042

journal_volume

6

pub_type

杂志文章
  • The two faces of autophagy: Coxiella and Mycobacterium.

    abstract::In the world of pathogen-host cell interactions, the autophagic pathway has been recently described as a component of the innate immune response against intracellular microorganisms. Indeed, some bacterial survival mechanisms are hampered when this process is activated. Mycobacterium tuberculosis infection of macropha...

    journal_title:Autophagy

    pub_type: 杂志文章,评审

    doi:10.4161/auto.2827

    authors: Colombo MI,Gutierrez MG,Romano PS

    更新日期:2006-07-01 00:00:00

  • Autophagy proteins play cytoprotective and cytocidal roles in leucine starvation-induced cell death in Saccharomyces cerevisiae.

    abstract::Autophagy is essential for prolonging yeast survival during nutrient deprivation; however, this report shows that some autophagy proteins may also be accelerating population death in those conditions. While leucine starvation caused YCA1-mediated apoptosis characterized by increased annexin V staining, nitrogen depriv...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.19314

    authors: Dziedzic SA,Caplan AB

    更新日期:2012-05-01 00:00:00

  • Purification of autophagosomes from rat hepatocytes.

    abstract::To facilitate the purification of rat liver autophagosomes, isolated rat hepatocytes are first incubated for 2 h at 37°C with vinblastine, which induces autophagosome accumulation by blocking the fusion of these organelles with endosomes and lysosomes. The hepatocytes are then electrodisrupted and homogenized, and the...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6.4.11272

    authors: Seglen PO,Brinchmann MF

    更新日期:2010-05-01 00:00:00

  • The GID ubiquitin ligase complex is a regulator of AMPK activity and organismal lifespan.

    abstract::The AMP-activated protein kinase (AMPK) regulates cellular energy homeostasis by sensing the metabolic status of the cell. AMPK is regulated by phosphorylation and dephosphorylation as a result of changing AMP/ATP levels and by removal of inhibitory ubiquitin residues by USP10. In this context, we identified the GID-c...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2019.1695399

    authors: Liu H,Ding J,Köhnlein K,Urban N,Ori A,Villavicencio-Lorini P,Walentek P,Klotz LO,Hollemann T,Pfirrmann T

    更新日期:2020-09-01 00:00:00

  • The glycolytic enzyme PFKFB3/phosphofructokinase regulates autophagy.

    abstract::T lymphocytes, the master regulators of immunity, have an unusual lifestyle. Equipped with a clonally distributed receptor they remain resting for long periods of time but go into overdrive when encountering antigen. Antigen recognition triggers an activation program that results in massive proliferation, differentiat...

    journal_title:Autophagy

    pub_type: 杂志文章,评审

    doi:10.4161/auto.27345

    authors: Yang Z,Goronzy JJ,Weyand CM

    更新日期:2014-02-01 00:00:00

  • SYK regulates macrophage MHC-II expression via activation of autophagy in response to oxidized LDL.

    abstract::Adaptive immunity, which plays an important role in the development of atherosclerosis, is mediated by major histocompatibility complex (MHC)-dependent antigen presentation. In atherosclerotic lesions, macrophages constitute an important class of antigen-presenting cells that activate adaptive immune responses to oxid...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2015.1037061

    authors: Choi SH,Gonen A,Diehl CJ,Kim J,Almazan F,Witztum JL,Miller YI

    更新日期:2015-01-01 00:00:00

  • Crocetin promotes clearance of amyloid-β by inducing autophagy via the STK11/LKB1-mediated AMPK pathway.

    abstract::Alzheimer disease (AD) is usually accompanied by two prominent pathological features, cerebral accumulation of amyloid-β (Aβ) plaques and presence of MAPT/tau neurofibrillary tangles. Dysregulated clearance of Aβ largely contributes to its accumulation and plaque formation in the brain. Macroautophagy/autophagy is a l...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2021.1872187

    authors: Wani A,Al Rihani SB,Sharma A,Weadick B,Govindarajan R,Khan SU,Sharma PR,Dogra A,Nandi U,Reddy CN,Bharate SS,Singh G,Bharate SB,Vishwakarma RA,Kaddoumi A,Kumar A

    更新日期:2021-01-19 00:00:00

  • How autophagy regulates the host cell signaling associated with the postpartum bacteria cocoon experienced as a danger signal.

    abstract::Shigella, the causative agent of human bacillary dysentery, invades the host cell, rapidly breaking the phagosome and multiplying in the cytosol. Here, we summarize our recent work showing the targeting of the leftover membrane remnants to autophagy together with trapped membrane-associated signaling molecules recruit...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.5.8.10218

    authors: Dupont N,Lafont F

    更新日期:2009-11-01 00:00:00

  • Clearance of a Hirano body-like F-actin aggresome generated by jasplakinolide.

    abstract::We have reported in a variety of mammalian cells the reversible formation of a filamentous actin (F-actin)-enriched aggresome generated by the actin toxin jasplakinolide (Lázaro-Diéguez et al., J Cell Sci 2008; 121:1415-25). Notably, this F-actin aggresome (FAG) resembles in many aspects the pathological Hirano body, ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6345

    authors: Lázaro-Diéguez F,Knecht E,Egea G

    更新日期:2008-07-01 00:00:00

  • FTY720-induced blockage of autophagy enhances anticancer efficacy of milatuzumab in mantle cell lymphoma: is FTY720 the next autophagy-blocking agent in lymphoma treatment?

    abstract::Inhibition of the autophagic pathway has recently revealed promising results in increasing pro-death activity of multiple cancer therapeutics. Here, we discuss our findings regarding the autophagy-blocking and anti-neoplastic effects of a synthetic sphingosine analog, FTY720, in mantle cell lymphoma (MCL). We also emp...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.19050

    authors: Alinari L,Baiocchi RA,Praetorius-Ibba M

    更新日期:2012-03-01 00:00:00

  • The interplay between PRKCI/PKCλ/ι, SQSTM1/p62, and autophagy orchestrates the oxidative metabolic response that drives liver cancer.

    abstract::Hepatocellular carcinoma (HCC) is the consequence of chronic liver damage caused by the excessive generation of reactive oxygen species (ROS). To mitigate the deleterious effects of ROS, cells activate the transcription factor NFE2L2/NRF2, which is constitutively degraded through its partner KEAP1. The inactivation of...

    journal_title:Autophagy

    pub_type: 评论,杂志文章

    doi:10.1080/15548627.2020.1797290

    authors: Moscat J,Diaz-Meco MT

    更新日期:2020-10-01 00:00:00

  • Intracellular Staphylococcus aureus eludes selective autophagy by activating a host cell kinase.

    abstract::Autophagy, a catabolic pathway of lysosomal degradation, acts not only as an efficient recycle and survival mechanism during cellular stress, but also as an anti-infective machinery. The human pathogen Staphylococcus aureus (S. aureus) was originally considered solely as an extracellular bacterium, but is now recogniz...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2016.1226732

    authors: Neumann Y,Bruns SA,Rohde M,Prajsnar TK,Foster SJ,Schmitz I

    更新日期:2016-11-01 00:00:00

  • SIRT5 regulation of ammonia-induced autophagy and mitophagy.

    abstract::In liver the mitochondrial sirtuin, SIRT5, controls ammonia detoxification by regulating CPS1, the first enzyme of the urea cycle. However, while SIRT5 is ubiquitously expressed, urea cycle and CPS1 are only present in the liver and, to a minor extent, in the kidney. To address the possibility that SIRT5 is involved i...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2015.1009778

    authors: Polletta L,Vernucci E,Carnevale I,Arcangeli T,Rotili D,Palmerio S,Steegborn C,Nowak T,Schutkowski M,Pellegrini L,Sansone L,Villanova L,Runci A,Pucci B,Morgante E,Fini M,Mai A,Russo MA,Tafani M

    更新日期:2015-01-01 00:00:00

  • Revisiting the role of autophagy in melanoma.

    abstract::Although alterations of the macroautophagy/autophagy-lysosome pathway have been observed in cancer for many years, the mechanisms underlying these changes and the importance of autophagic and lysosomal reprogramming by cancer have yet to be well identified. Our recent study demonstrates that oncogenic BRAF signaling p...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2019.1635386

    authors: Li S,Song Y,Quach C,Nemecio D,Liang C

    更新日期:2019-10-01 00:00:00

  • Autophagy and innate immunity: Insights from invertebrate model organisms.

    abstract::Macroautophagy/autophagy is a fundamental intracellular degradation process with multiple roles in immunity, including direct elimination of intracellular microorganisms via 'xenophagy.' In this review, we summarize studies from the fruit fly Drosophila melanogaster and the nematode Caenorhabditis elegans that highlig...

    journal_title:Autophagy

    pub_type: 杂志文章,评审

    doi:10.1080/15548627.2017.1389824

    authors: Kuo CJ,Hansen M,Troemel E

    更新日期:2018-01-01 00:00:00

  • Mutant HTT (huntingtin) impairs mitophagy in a cellular model of Huntington disease.

    abstract::The precise degradation of dysfunctional mitochondria by mitophagy is essential for maintaining neuronal homeostasis. HTT (huntingtin) can interact with numerous other proteins and thereby perform multiple biological functions within the cell. In this study, we investigated the role of HTT during mitophagy and analyze...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2020.1728096

    authors: Franco-Iborra S,Plaza-Zabala A,Montpeyo M,Sebastian D,Vila M,Martinez-Vicente M

    更新日期:2020-02-24 00:00:00

  • Localized de novo phospholipid synthesis drives autophagosome biogenesis.

    abstract::During (macro)autophagy, cells form transient organelles, termed autophagosomes, to target a broad spectrum of substrates for degradation critical to cellular and organismal health. Driven by rapid membrane assembly, an initially small vesicle (phagophore) elongates into a large cup-shaped structure to engulf substrat...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2020.1725379

    authors: Schütter M,Graef M

    更新日期:2020-04-01 00:00:00

  • A sensitive and quantitative autolysosome probe for detecting autophagic activity in live and prestained fixed cells.

    abstract::Autophagy is a complex, multi-step and biologically important pathway mediated by autophagosomes and autolysosomes. Accurately dissecting and detecting different stages of autophagy is important to elucidate its molecular mechanism and thereby facilitate the discovery of pharmaceutical molecules. We herein reported a ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.24241

    authors: Chen JJ,Jing J,Chang H,Rong Y,Hai Y,Tang J,Zhang JL,Xu P

    更新日期:2013-06-01 00:00:00

  • Regulation of JMY's actin nucleation activity by TTC5/STRAP and LC3 during autophagy.

    abstract::Actin plays indispensable roles in autophagosome biogenesis. Branched actin networks assembled within phagophore membranes are required for generating the autophagosome membrane shape and movement. The ARP2/3 complex and its regulators, such as JMY (junction mediating and regulatory protein, p53 cofactor), translocate...

    journal_title:Autophagy

    pub_type: 评论,社论

    doi:10.1080/15548627.2018.1564417

    authors: Liu X,Klionsky DJ

    更新日期:2019-03-01 00:00:00

  • Bacillus calmette-guerin cell wall cytoskeleton enhances colon cancer radiosensitivity through autophagy.

    abstract::The cell wall skeleton of Mycobacterium bovis Bacillus Calmette-Guerin (BCG/CWS) is an effective antitumor immunotherapy agent. Here, we demonstrate that BCG/CWS has a radiosensitizing effect on colon cancer cells through the induction of autophagic cell death. Exposure of HCT116 colon cancer cells to BCG/CWS before i...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6.1.10325

    authors: Yuk JM,Shin DM,Song KS,Lim K,Kim KH,Lee SH,Kim JM,Lee JS,Paik TH,Kim JS,Jo EK

    更新日期:2010-01-01 00:00:00

  • Silencing of Bcl-2 expression by small interfering RNA induces autophagic cell death in MCF-7 breast cancer cells.

    abstract::Apoptosis (programmed cell death type I) and autophagy (type II) are crucial mechanisms regulating cell death and homeostasis. The Bcl-2 proto-oncogene is overexpressed in 50-70% of breast cancers, potentially leading to resistance to chemotherapy, radiation and hormone therapy-induced apoptosis. Here, we investigated...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6083

    authors: Akar U,Chaves-Reyez A,Barria M,Tari A,Sanguino A,Kondo Y,Kondo S,Arun B,Lopez-Berestein G,Ozpolat B

    更新日期:2008-07-01 00:00:00

  • MLKL contributes to Western diet-induced liver injury through inhibiting autophagy.

    abstract::Macroautophagy/autophagy is critical in maintaining cellular functions and homeostasis. Dynamic regulation of autophagy is associated with development of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH); however, the mechanisms involved in the regulation of autophagy in NAFLD/NASH are n...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2020.1760624

    authors: Wu X,Nagy LE

    更新日期:2020-07-01 00:00:00

  • UVRAG: at the crossroad of autophagy and genomic stability.

    abstract::UVRAG is a promoter of the autophagy pathway, and its deficiency may fuel the development of cancers. Intriguingly, our recent study has demonstrated that this protein also mediates the repair of damaged DNA and patrols centrosome stability, mechanisms that commonly prevent cancer progression, in a manner independent ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.21035

    authors: Zhao Z,Ni D,Ghozalli I,Pirooz SD,Ma B,Liang C

    更新日期:2012-09-01 00:00:00

  • How to interpret LC3 immunoblotting.

    abstract::Microtubule-associated protein light chain 3 (LC3) is now widely used to monitor autophagy. One approach is to detect LC3 conversion (LC3-I to LC3-II) by immunoblot analysis because the amount of LC3-II is clearly correlated with the number of autophagosomes. However, LC3-II itself is degraded by autophagy, making int...

    journal_title:Autophagy

    pub_type: 杂志文章,评审

    doi:10.4161/auto.4600

    authors: Mizushima N,Yoshimori T

    更新日期:2007-11-01 00:00:00

  • Autophagy proteins promote hepatitis C virus replication.

    abstract::Autophagy is a fundamental process for anti-viral defense. Not surprisingly, viruses have developed strategies to subvert or use autophagy for their own benefit. In cell culture, autophagy proteins are proviral factors that favor initiation of hepatitis C virus (HCV) infection. Autophagy proteins are required for tran...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.5.8.10219

    authors: Dreux M,Chisari FV

    更新日期:2009-11-01 00:00:00

  • Decreased insulin-receptor signaling promotes the autophagic degradation of beta-amyloid peptide in C. elegans.

    abstract::Autophagy is a conserved membrane trafficking pathway that mediates the delivery of cytoplasmic substrates to the lysosome for degradation. Impaired autophagic function is implicated in the pathology of various neurodegenerative diseases. We have generated transgenic C. elegans that express human beta-amyloid peptide ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.4776

    authors: Florez-McClure ML,Hohsfield LA,Fonte G,Bealor MT,Link CD

    更新日期:2007-11-01 00:00:00

  • An insight into the mechanistic role of p53-mediated autophagy induction in response to proteasomal inhibition-induced neurotoxicity.

    abstract::The ubiquitin-proteasome system (UPS) and the autophagy-lysosomal pathway (ALP) are the two most important components of cellular mechanisms for protein degradation. In the present study we investigated the functional relationship of the two systems and the interactional role of p53 in vitro. Our study showed that the...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.5.5.8377

    authors: Du Y,Yang D,Li L,Luo G,Li T,Fan X,Wang Q,Zhang X,Wang Y,Le W

    更新日期:2009-07-01 00:00:00

  • The next generation proteasome inhibitors carfilzomib and oprozomib activate prosurvival autophagy via induction of the unfolded protein response and ATF4.

    abstract::The proteasome inhibitor bortezomib has shown remarkable clinical success in the treatment of multiple myeloma. However, the efficacy and mechanism of action of bortezomib in solid tumor malignancies is less well understood. In addition, the use of this first-in-class proteasome inhibitor is limited by several factors...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.22185

    authors: Zang Y,Thomas SM,Chan ET,Kirk CJ,Freilino ML,DeLancey HM,Grandis JR,Li C,Johnson DE

    更新日期:2012-12-01 00:00:00

  • Anti-neoplastic activity of the cytosolic FoxO1 results from autophagic cell death.

    abstract::Although Beclin 1 and mTOR are considered to be the main molecules to modulate the autophagic process, searching for other autophagy-regulating molecules is still an ongoing challenge to scientists. Here we demonstrated that FoxO1, a forkhead O family protein, is a mediator of autophagy. Upon oxidative stress or serum...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6.7.13289

    authors: Zhao Y,Wang L,Yang J,Zhang P,Ma K,Zhou J,Liao W,Zhu WG

    更新日期:2010-10-01 00:00:00

  • Quercetin induces protective autophagy in gastric cancer cells: involvement of Akt-mTOR- and hypoxia-induced factor 1α-mediated signaling.

    abstract::Quercetin, a dietary antioxidant present in fruits and vegetables, is a promising cancer chemopreventive agent that inhibits tumor promotion by inducing cell cycle arrest and promoting apoptotic cell death. In this study, we examined the biological activities of quercetin against gastric cancer. Our studies demonstrat...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.7.9.15863

    authors: Wang K,Liu R,Li J,Mao J,Lei Y,Wu J,Zeng J,Zhang T,Wu H,Chen L,Huang C,Wei Y

    更新日期:2011-09-01 00:00:00