Autophagy and access: understanding the role of androgen receptor subcellular localization in SBMA.

Abstract:

:Ridding neurons of toxic misfolded proteins is a critical feature of many neurodegenerative diseases. We have recently reported that lack of access of nuclear polyglutamine-expanded androgen receptor (AR) to the autophagic degradation pathway is a critical point in pathogenesis. When mutant AR is contained within the cytoplasm, it can be degraded by autophagy, resulting in amelioration of its toxic effects, as has been observed in other polyglutamine expansion diseases involving cytoplasmic mutant proteins. However, we have also found that pharmacological induction of autophagy protects SBMA motor neurons from the toxic effects of even nuclear localized mutant AR, albeit without affecting mutant nuclear AR levels. Thus, we have further investigated the mechanism by which autophagy elicits therapeutic benefit in cell culture. We found that endogenous autophagy only slightly alters nuclear mutant AR aggregation compared to substantial effects on cytoplasmic AR aggregation. Interestingly, pharmacological activation of mTOR-dependent autophagy did not significantly alter nuclear AR aggregation, whereas we observed that it protects SBMA motor neurons. Our findings indicate that therapeutic intervention to induce autophagy represents a potential potent benefit for SBMA, and that it likely does so by protecting SBMA motor neurons independent of a direct effect on mutant AR.

journal_name

Autophagy

journal_title

Autophagy

authors

Montie HL,Merry DE

doi

10.4161/auto.5.8.9726

subject

Has Abstract

pub_date

2009-11-01 00:00:00

pages

1194-7

issue

8

eissn

1554-8627

issn

1554-8635

pii

9726

journal_volume

5

pub_type

杂志文章
  • Restoring autophagic flux attenuates cochlear spiral ganglion neuron degeneration by promoting TFEB nuclear translocation via inhibiting MTOR.

    abstract::Macroautophagy/autophagy dysfunction is associated with many neurodegenerative diseases. TFEB (transcription factor EB), an important molecule that regulates lysosomal and autophagy function, is regarded as a potential target for treating some neurodegenerative diseases. However, the relationship between autophagy dys...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2019.1569926

    authors: Ye B,Wang Q,Hu H,Shen Y,Fan C,Chen P,Ma Y,Wu H,Xiang M

    更新日期:2019-06-01 00:00:00

  • PARK2-mediated mitophagy is involved in regulation of HBEC senescence in COPD pathogenesis.

    abstract::Cigarette smoke (CS)-induced mitochondrial damage with increased reactive oxygen species (ROS) production has been implicated in COPD pathogenesis by accelerating senescence. Mitophagy may play a pivotal role for removal of CS-induced damaged mitochondria, and the PINK1 (PTEN-induced putative kinase 1)-PARK2 pathway h...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2015.1017190

    authors: Ito S,Araya J,Kurita Y,Kobayashi K,Takasaka N,Yoshida M,Hara H,Minagawa S,Wakui H,Fujii S,Kojima J,Shimizu K,Numata T,Kawaishi M,Odaka M,Morikawa T,Harada T,Nishimura SL,Kaneko Y,Nakayama K,Kuwano K

    更新日期:2015-01-01 00:00:00

  • The Thr300Ala variant of ATG16L1 is associated with decreased risk of brain metastasis in patients with non-small cell lung cancer.

    abstract::Non-small cell lung cancer (NSCLC) often metastasizes to the brain, but identifying which patients will develop brain metastases (BM) is difficult. Macroautophagy/autophagy is critical for cancer initiation and progression. We hypothesized that genetic variants of autophagy-related genes may affect brain metastases (B...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2017.1308997

    authors: Li QX,Zhou X,Huang TT,Tang Y,Liu B,Peng P,Sun L,Wang YH,Yuan XL

    更新日期:2017-06-03 00:00:00

  • Autophagy in nuclear receptor PPARgamma-deficient mouse prostatic carcinogenesis.

    abstract::Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a major modulator of cellular lipid metabolism and organelle differentiation. To understand whether autophagy is involved in the processes of dysregulated fatty acid oxidation and induced oxidative stress accompanying prostatic carcinogenesis, we characte...

    journal_title:Autophagy

    pub_type: 杂志文章,评审

    doi:10.4161/auto.6.1.10700

    authors: Jiang M,Jerome WG,Hayward SW

    更新日期:2010-01-01 00:00:00

  • Cocaine-mediated microglial activation involves the ER stress-autophagy axis.

    abstract::Cocaine abuse leads to neuroinflammation, which, in turn, contributes to the pathogenesis of neurodegeneration associated with advanced HIV-1 infection. Autophagy plays important roles in both innate and adaptive immune responses. However, the possible functional link between cocaine and autophagy has not been explore...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2015.1052205

    authors: Guo ML,Liao K,Periyasamy P,Yang L,Cai Y,Callen SE,Buch S

    更新日期:2015-01-01 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

  • Histone deacetylase 10-promoted autophagy as a druggable point of interference to improve the treatment response of advanced neuroblastomas.

    abstract::Neuroblastoma is the most common extracranial solid tumor in childhood. Despite intense multimodal therapy and many improvements through basic scientific and clinical research, the successful response of advanced-stage patients to chemotherapy remains poor. Autophagy is a cytoprotective mechanism that may help advance...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.26450

    authors: Oehme I,Lodrini M,Brady NR,Witt O

    更新日期:2013-12-01 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

  • Mutation at the cargo-receptor binding site of Atg8 also affects its general autophagy regulation function.

    abstract::Autophagy is a highly conserved degradation pathway for intracellular macromolecules and organelles. Among those characterized autophagy regulators, the ubiquitin-like protein Atg8 is found to be a membrane modifier that both regulates biogenesis of transport vesicles and interacts with the cargo receptor Atg19 for se...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.5.4.7696

    authors: Ho KH,Chang HE,Huang WP

    更新日期:2009-05-01 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

  • 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

  • Targeted therapy for the loss of von Hippel-Lindau in renal cell carcinoma: a novel molecule that induces autophagic cell death.

    abstract::Radiation and conventional cytotoxic chemotherapies are ineffective in treating renal cancer. Approximately 75 percent of renal cell carcinoma (RCC) is associated with an inactivation of the tumor suppressor gene von Hippel-Lindau (VHL). We exploited the possibility of targeting VHL-deficient RCC through synthetic let...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6785

    authors: Turcotte S,Sutphin PD,Giaccia AJ

    更新日期:2008-10-01 00:00:00

  • Sorting cells for basal and induced autophagic flux by quantitative ratiometric flow cytometry.

    abstract::We detail here a protocol using tandem-tagged mCherry-EGFP-LC3 (C-G-LC3) to quantify autophagic flux in single cells by ratiometric flow cytometry and to isolate subpopulations of cells based on their relative levels of autophagic flux. This robust and sensitive method measures autophagic flux rather than autophagosom...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.29394

    authors: Gump JM,Thorburn A

    更新日期:2014-07-01 00:00:00

  • Autophagy fosters myofibroblast differentiation through MTORC2 activation and downstream upregulation of CTGF.

    abstract::Recent evidence suggests that autophagy may favor fibrosis through enhanced differentiation of fibroblasts in myofibroblasts. Here, we sought to characterize the mediators and signaling pathways implicated in autophagy-induced myofibroblast differentiation. Fibroblasts, serum starved for up to 4 d, showed increased LC...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/15548627.2014.981786

    authors: Bernard M,Dieudé M,Yang B,Hamelin K,Underwood K,Hébert MJ

    更新日期:2014-01-01 00:00:00

  • The TOMM machinery is a molecular switch in PINK1 and PARK2/PARKIN-dependent mitochondrial clearance.

    abstract::Loss-of-function mutations in PARK2/PARKIN and PINK1 cause early-onset autosomal recessive Parkinson disease (PD). The cytosolic E3 ubiquitin-protein ligase PARK2 cooperates with the mitochondrial kinase PINK1 to maintain mitochondrial quality. A loss of mitochondrial transmembrane potential (ΔΨ) leads to the PINK1-de...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.25884

    authors: Bertolin G,Ferrando-Miguel R,Jacoupy M,Traver S,Grenier K,Greene AW,Dauphin A,Waharte F,Bayot A,Salamero J,Lombès A,Bulteau AL,Fon EA,Brice A,Corti O

    更新日期:2013-11-01 00:00:00

  • Autophagy contributes to regulation of nuclear dynamics during vegetative growth and hyphal fusion in Fusarium oxysporum.

    abstract::In the fungal pathogen Fusarium oxysporum, vegetative hyphal fusion triggers nuclear mitotic division in the invading hypha followed by migration of a nucleus into the receptor hypha and degradation of the resident nucleus. Here we examined the role of autophagy in fusion-induced nuclear degradation. A search of the F...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/15548627.2014.994413

    authors: Corral-Ramos C,Roca MG,Di Pietro A,Roncero MI,Ruiz-Roldán C

    更新日期:2015-01-01 00:00:00

  • Autophagy and heterophagy dysregulation leads to retinal pigment epithelium dysfunction and development of age-related macular degeneration.

    abstract::Age-related macular degeneration (AMD) is a complex, degenerative and progressive eye disease that usually does not lead to complete blindness, but can result in severe loss of central vision. Risk factors for AMD include age, genetics, diet, smoking, oxidative stress and many cardiovascular-associated risk factors. A...

    journal_title:Autophagy

    pub_type: 杂志文章,评审

    doi:10.4161/auto.24546

    authors: Kaarniranta K,Sinha D,Blasiak J,Kauppinen A,Veréb Z,Salminen A,Boulton ME,Petrovski G

    更新日期:2013-07-01 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

  • Tomato HsfA1a plays a critical role in plant drought tolerance by activating ATG genes and inducing autophagy.

    abstract::Autophagy plays critical roles in plant responses to stress. In contrast to the wealth of information concerning the core process of plant autophagosome assembly, our understanding of the regulation of autophagy is limited. In this study, we demonstrated that transcription factor HsfA1a played a critical role in tomat...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2015.1098798

    authors: Wang Y,Cai S,Yin L,Shi K,Xia X,Zhou Y,Yu J,Zhou J

    更新日期:2015-11-02 00:00:00

  • Macroautophagy-dependent, intralysosomal cleavage of a betaine homocysteine methyltransferase fusion protein requires stable multimerization.

    abstract::Cargo-based assays have proven invaluable in the study of macroautophagy in yeast and mammalian cells. Proteomic analysis of autolysosomes identified the metabolic enzyme, betaine homocysteine methyltransferase (BHMT), as a potential cargo-based, end-point marker for mammalian macroautophagy. To test whether degradati...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.5275

    authors: Mercer CA,Kaliappan A,Dennis PB

    更新日期:2008-02-01 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

  • Role of Arabidopsis RabG3b and autophagy in tracheary element differentiation.

    abstract::The vascular system of plants consists of two conducting tissues, xylem and phloem, which differentiate from procambium cells. Xylem serves as a transporting system for water and signaling molecules and is formed by sequential developmental processes, including cell division/expansion, secondary cell wall deposition, ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6.8.13429

    authors: Kwon SI,Cho HJ,Park OK

    更新日期:2010-11-01 00:00:00

  • Heme and iron induce protein aggregation.

    abstract::Heme is an essential molecule expressed in many tissues where it plays key roles as the prosthetic group of several proteins involved in vital physiological and metabolic processes such as gas and electron transport. Structurally, heme is a tetrapyrrole ring containing an atom of iron (Fe) in its center. When released...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.1080/15548627.2016.1271515

    authors: Travassos LH,Vasconcellos LR,Bozza MT,Carneiro LA

    更新日期:2017-03-04 00:00:00

  • Autophagy modulates SNCA/α-synuclein release, thereby generating a hostile microenvironment.

    abstract::SNCA/α-synuclein aggregation plays a crucial role in synucleinopathies such as Parkinson disease and dementia with Lewy bodies. Aggregating and nonaggregating SNCA species are degraded by the autophagy-lysosomal pathway (ALP). Previously, we have shown that the ALP is not only responsible for SNCA degradation but is a...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.36436

    authors: Poehler AM,Xiang W,Spitzer P,May VE,Meixner H,Rockenstein E,Chutna O,Outeiro TF,Winkler J,Masliah E,Klucken J

    更新日期:2014-01-01 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

  • A novel quantitative flow cytometry-based assay for autophagy.

    abstract::Autophagy is a cellular degradation process with an increasingly recognised importance in many biological pathways such as nutrient sensing, stress responses and development. We present a straightforward assay for autophagy which combines the sensitivity of the EGFP-LC3 reporter protein with the throughput capacity an...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6.5.12112

    authors: Eng KE,Panas MD,Karlsson Hedestam GB,McInerney GM

    更新日期:2010-07-01 00:00:00

  • 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 neu...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.6.7.13042

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

    更新日期:2010-10-01 00:00:00

  • When more is less: excess and deficiency of autophagy coexist in skeletal muscle in Pompe disease.

    abstract::The role of autophagy, a catabolic lysosome-dependent pathway, has recently been recognized in a variety of disorders, including Pompe disease, which results from a deficiency of the glycogen-degrading lysosomal hydrolase acid-alpha glucosidase (GAA). Skeletal and cardiac muscle are most severely affected by the progr...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.5.1.7293

    authors: Raben N,Baum R,Schreiner C,Takikita S,Mizushima N,Ralston E,Plotz P

    更新日期:2009-01-01 00:00:00

  • Induction of autophagy by drug-resistant esophageal cancer cells promotes their survival and recovery following treatment with chemotherapeutics.

    abstract::We investigated the cell-death mechanisms induced in esophageal cancer cells in response to the chemotherapeutic drugs, 5-fluorouracil (5-FU) and cisplatin. Chemosensitive cell lines exhibited apoptosis whereas chemoresistant populations exhibited autophagy and a morphology resembling type II programmed cell death (PC...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.7.6.15066

    authors: O'Donovan TR,O'Sullivan GC,McKenna SL

    更新日期:2011-05-01 00:00:00

  • Denervation-induced oxidative stress and autophagy signaling in muscle.

    abstract::Alterations in contractile activity influence the intracellular homeostasis of muscle, which results in adaptations in the performance and the phenotype of this tissue. Denervation is an effective disuse model that functions to change the intracellular environment of muscle leading to a rapid loss in mass, a decrease ...

    journal_title:Autophagy

    pub_type: 杂志文章

    doi:10.4161/auto.5.2.7391

    authors: O'Leary MF,Hood DA

    更新日期:2009-02-01 00:00:00