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Condition: Ataxia

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Total 67 results found since Jan 2013.

Prelamin a accelerates vascular calcification via activation of the DNA damage response and senescence-associated secretory phenotype in vascular smooth muscle cells.
Conclusions: Prelamin A promotes VSMC calcification and aging by inducing persistent DNA damage signaling, which acts upstream of VSMC osteogenic differentiation and the senescence-associated secretory phenotype. Agents that target the DNA damage response and prelamin A toxicity may be potential therapies for the treatment of vascular calcification. PMID: 23564641 [PubMed - in process]
Source: Circulation Research - May 10, 2013 Category: Cardiology Authors: Liu Y, Drozdov I, Shroff R, Beltran LE, Shanahan CM Tags: Circ Res Source Type: research

Nuclear Import of HBXIP Requires Collaboration with c-Fos Gene Regulation
Aberrant nuclear localization of oncogenic transcription factors and coactivators always leads to the development of cancer. We have reported that the oncoprotein hepatitis B X-interacting protein (HBXIP) acts as a novel transcriptional coactivator to promote proliferation and migration of breast cancer cells. However, the mechanism of regulating the nuclear import of HBXIP remains unclear. In the present study, we found that HBXIP interacted with c-Fos through their leucine zipper domains in vitro and in vivo. Interestingly, the leucine zipper mutant of HBXIP (or c-Fos) was unavailable to bind to c-Fos (or HBXIP), resulti...
Source: Journal of Biological Chemistry - June 28, 2013 Category: Chemistry Authors: Zhang, Y., Zhao, Y., Li, H., Li, Y., Cai, X., Shen, Y., Shi, H., Li, L., Liu, Q., Zhang, X., Ye, L. Tags: Cell Biology Source Type: research

Mutant γPKC that causes spinocerebellar ataxia type 14 upregulates Hsp70, which protects cells from the mutant's cytotoxicity.
Abstract Several missense mutations in the protein kinase Cγ (γPKC) gene have been found to cause spinocerebellar ataxia type 14 (SCA14), an autosomal dominant neurodegenerative disease. We previously demonstrated that the mutant γPKC found in SCA14 is misfolded, susceptible to aggregation and cytotoxic. Molecular chaperones assist the refolding and degradation of misfolded proteins and prevention of the proteins' aggregation. In the present study, we found that the expression of mutant γPKC-GFP increased the levels of heat-shock protein 70 (Hsp70) in SH-SY5Y cells. To elucidate the role of this elevation, we ...
Source: Biochemical and Biophysical Research communications - September 7, 2013 Category: Biochemistry Authors: Ogawa K, Seki T, Onji T, Adachi N, Tanaka S, Hide I, Saito N, Sakai N Tags: Biochem Biophys Res Commun Source Type: research

Prodegenerative IκBα expression in oligodendroglial α-synuclein models of multiple system atrophy.
Abstract Multiple system atrophy is a progressive, neurodegenerative disease characterized by parkinsonism, ataxia, autonomic dysfunction, and accumulation of α-synuclein in oligodendrocytes. To understand how α-synuclein aggregates impact oligodendroglial homeostasis, we investigated an oligodendroglial cell model of α-synuclein dependent degeneration and identified responses linked to the NF-κB transcription factor stress system. Coexpression of human α-synuclein and the oligodendroglial protein p25α increased the expression of IκBα mRNA and protein early during the degenerative process and this was depe...
Source: Neurobiology of Disease - December 17, 2013 Category: Neurology Authors: Kragh CL, Gysbers AM, Rockenstein E, Murphy K, Halliday GM, Masliah E, Jensen PH Tags: Neurobiol Dis Source Type: research

cAMP signaling inhibits radiation-induced ATM phosphorylation leading to the augmentation of apoptosis in human lung cancer cells
Conclusions: cAMP signaling inhibits radiation-induced ATM activation by PKA-dependent activation of PP2A, and this signaling mechanism augments radiation-induced apoptosis by reducing ATM-dependent activation of NF-kappaB in lung cancer cells.
Source: Molecular Cancer - February 24, 2014 Category: Cancer & Oncology Authors: Eun-Ah ChoEui-Jun KimSahng-June KwakYong-Sung Juhnn Source Type: research

Coenzyme Q10, Statin, and Spinocerebellar Ataxias (P6.047)
CONCLUSIONS:CoQ10 is associated with better clinical outcome in SCA1, 2, and 3 whereas statins are associated with worse clinical outcome in SCA6. These drug exposures did not appear to influence clinical progression within 2 years. CoQ10 and statins may have only symptomatic effects or require a longer period of time for disease modification.Study Supported by:American Brain Foundation Research Fellowship, Rare Disease Clinical Research Network RC1NS068897, and NINDS K08 NS083738.Disclosure: Dr. Kuo has nothing to disclose. Dr. Lo has nothing to disclose. Dr. Figueroa has nothing to disclose. Dr. Pulst has received person...
Source: Neurology - April 9, 2014 Category: Neurology Authors: Kuo, S.-H., Lo, R., Figueroa, K., Pulst, S., Perlman, S., Wilmot, G., Gomez, C., Schmahmann, J., Paulson, H., Shakkottai, V., Ying, S., Zesiewicz, T., Bushara, K., Geschwind, M., Xia, G., Subramony, S., Ashizawa, T. Tags: Movement Disorders: Spinocerebellar Ataxias Source Type: research

Coenzyme Q10, Statin, and Spinocerebellar Ataxias (I11-1.008)
CONCLUSIONS:CoQ10 is associated with better clinical outcome in SCA1, 2, and 3 whereas statins are associated with worse clinical outcome in SCA6. These drug exposures did not appear to influence clinical progression within 2 years. CoQ10 and statins may have only symptomatic effects or require a longer period of time for disease modification.Study Supported by:American Brain Foundation Research Fellowship, Rare Disease Clinical Research Network RC1NS068897, and NINDS K08 NS083738.Disclosure: Dr. Kuo has nothing to disclose. Dr. Lo has nothing to disclose. Dr. Figueroa has nothing to disclose. Dr. Pulst has received person...
Source: Neurology - April 9, 2014 Category: Neurology Authors: Kuo, S.-H., Lo, R., Figueroa, K., Pulst, S., Perlman, S., Wilmot, G., Gomez, C., Schmahmann, J., Paulson, H., Shakkottai, V., Ying, S., Zesiewicz, T., Bushara, K., Geschwind, M., Xia, G., Subramony, S., Ashizawa, T. Tags: Proteinopathy in Neurodegenerative Disease Poster Presentations Source Type: research

An ATM-MPG Axis Promotes Resistance to Alkylating Agents Research Articles
This article is highlighted in the In This Issue feature, p. 1103
Source: Cancer Discovery - September 30, 2014 Category: Cancer & Oncology Authors: Agnihotri, S., Burrell, K., Buczkowicz, P., Remke, M., Golbourn, B., Chornenkyy, Y., Gajadhar, A., Fernandez, N. A., Clarke, I. D., Barszczyk, M. S., Pajovic, S., Ternamian, C., Head, R., Sabha, N., Sobol, R. W., Taylor, M. D., Rutka, J. T., Jones, C., Di Tags: Preclinical Intervention, Preclinical Intervention: In Vitro: Drugs, Mechanisms Research Articles Source Type: research

The catalytic topoisomerase II inhibitor dexrazoxane induces DNA breaks, ATF3 and the DNA damage response in cancer cells
Conclusions and ImplicationsSimilar to TOP2A poisons, DRZ induces DNA double‐strand breaks followed by activation of DNA damage response. The DNA damage‐triggered ATF3 controls the level of p53 accumulation as well as double‐strand breaks generation and is proposed to serve as a switch between DNA damage and cell death following DRZ treatment. These findings suggest a mechanistic explanation for the diverse clinical observations associated with DRZ.
Source: British Journal of Pharmacology - December 17, 2014 Category: Drugs & Pharmacology Authors: Shiwei Deng, Tiandong Yan, Teodora Nikolova, Dominik Fuhrmann, Andrea Nemecek, Ute Gödtel‐Armbrust, Bernd Kaina, Leszek Wojnowski Tags: Research Paper Source Type: research

ATR and ATM Loss-of-Function
Mechanisms to maintain genomic integrity are essential for cells to remain viable. Not surprisingly, disruption of key DNA damage response pathway factors, such as ataxia telangiectasia-mutated (ATM)/ataxia telangiectasia and RAD3-related (ATR) results in loss of genomic integrity. Here, a synthetic lethal siRNA-screening approach not only confirmed ATM but identified additional replication checkpoint proteins, when ablated, enhanced ATR inhibitor (ATRi) response in a high-content -H2AX assay. Cancers with inactivating ATM mutations exhibit impaired DNA double-stranded break (DSB) repair and rely on compensatory repair pat...
Source: Molecular Cancer Research - January 15, 2015 Category: Cancer & Oncology Authors: Menezes, D. L., Holt, J., Tang, Y., Feng, J., Barsanti, P., Pan, Y., Ghoddusi, M., Zhang, W., Thomas, G., Holash, J., Lees, E., Taricani, L. Tags: DNA Damage and Repair Source Type: research

Resveratrol analogue (E)-8-acetoxy-2-2-(3,4-diacetoxyphenyl)ethenyl-quinazoline induces G2/M cell cycle arrest through the activation of ATM/ATR in human cervical carcinoma HeLa cells.
Authors: Kim JY, Choi HE, Lee HH, Shin JS, Shin DH, Choi JH, Lee YS, Lee KT Abstract Styrylquinazolines are synthetic analogues of resveratrol and have been suggested to cause anti-inflammatory activity by modulating prostaglandin E2 (PGE2) production. In the present study, we evaluated cytotoxic effects of various styrylquinazoline derivatives and found that (E)-8-acetoxy-2-[2-(3,4-diacetoxyphenyl)ethenyl]-quinazoline (8-ADEQ) most potently inhibited the proliferation of the human cervical carcinoma HeLa cells. Exploring the growth-inhibitory mechanisms of 8-ADEQ, we found that it causes a cell cycle arrest at the...
Source: Oncology Reports - April 1, 2015 Category: Cancer & Oncology Tags: Oncol Rep Source Type: research

PTEN-Deficient Tumor Cells Are Dependent on ATM Signaling
In this study, we took an siRNA screening strategy to identify other tumor suppressors that, when inhibited, similarly sensitized cells to ATM inhibition. In this manner, we determined that PTEN and ATM were synthetically lethal when jointly inhibited. PTEN-deficient cells exhibited elevated levels of reactive oxygen species, increased endogenous DNA damage, and constitutive ATM activation. ATM inhibition caused catastrophic DNA damage, mitotic cell cycle arrest, and apoptosis specifically in PTEN-deficient cells in comparison with wild-type cells. Antioxidants abrogated the increase in DNA damage and ATM activation in PTE...
Source: Cancer Research - May 31, 2015 Category: Cancer & Oncology Authors: McCabe, N., Hanna, C., Walker, S. M., Gonda, D., Li, J., Wikstrom, K., Savage, K. I., Butterworth, K. T., Chen, C., Harkin, D. P., Prise, K. M., Kennedy, R. D. Tags: Priority Reports Source Type: research

Genome-Engineering Tools to Establish Accurate Reporter Cell Lines That Enable Identification of Therapeutic Strategies to Treat Friedreich's Ataxia
Friedreich’s ataxia is a neurodegenerative disease caused by deficiency of the mitochondrial protein frataxin. This deficiency results from expansion of a trinucleotide repeat in the first intron of the frataxin gene. Because this repeat expansion resides in an intron and hence does not alter the amino acid sequence of the frataxin protein, gene reactivation could be of therapeutic benefit. High-throughput screening for frataxin activators has so far met with limited success because current cellular models may not accurately assess endogenous frataxin gene regulation. Here we report the design and validation of genom...
Source: Journal of Biomolecular Screening - June 19, 2015 Category: Molecular Biology Authors: Villasenor, R., Miraglia, L., Romero, A., Tu, B., Punga, T., Knuckles, P., Duss, S., Orth, T., Buhler, M. Tags: Original Research Source Type: research

Abstract 5193: Ataxia telangiectasia mutated relates to epithelial-mesenchymal transition in colorectal cancer
Conclusions: ATM might be a critical regulator of EMT in colorectal cancer invasion.Citation Format: Hidena Takahashi, Masashi Tsuruta, Hirotoshi Hasegawa, Koji Okabayashi, Ryo Seishima, Shimpei Matsui, Toru Yamada, Takayuki Kondo, Takehiro Shimada, Mutsuhito Matsuda, Masashi Yahagi, Yusuke Yoshikawa, Yusuke Asada, Kiyoaki Sugiura, Yoshiyuki Suzuki, Yuki Tajima, Junpei Nakadai, Yuko Kitagawa. Ataxia telangiectasia mutated relates to epithelial-mesenchymal transition in colorectal cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Takahashi, H., Tsuruta, M., Hasegawa, H., Okabayashi, K., Seishima, R., Matsui, S., Yamada, T., Kondo, T., Shimada, T., Matsuda, M., Yahagi, M., Yoshikawa, Y., Asada, Y., Sugiura, K., Suzuki, Y., Tajima, Y., Nakadai, J., Kitagawa, Y. Tags: Tumor Biology Source Type: research

Phenotypic Screening for Friedreich Ataxia Using Random shRNA Selection
Friedreich ataxia (FRDA) is an autosomal recessive neuro- and cardio-degenerative disorder for which there are no proven effective treatments. FRDA is caused by decreased expression and/or function of the protein frataxin. Frataxin chaperones iron in the mitochondrial matrix and regulates the iron–sulfur cluster (ISC) assembly complex. ISCs are prosthetic groups critical for the function of the Krebs cycle and the mitochondrial electron transport chain. Decreased expression of frataxin is associated with decreased ISC assembly, mitochondrial iron accumulation, and increased oxidative stress, all of which contribute t...
Source: Journal of Biomolecular Screening - September 18, 2015 Category: Molecular Biology Authors: Cotticelli, M. G., Acquaviva, F., Xia, S., Kaur, A., Wang, Y., Wilson, R. B. Tags: Original Research Source Type: research