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Coyne, Alyssa N

0000-0002-3658-5325

Mayo Clinic

Robert Packard Center for ALS Research, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21205, USA.

Citations 3

Poly(ADP-ribose) promotes toxicity of C9ORF72 arginine-rich dipeptide repeat proteins
Gao, Junli , Mewborne, Quinlan T. , Girdhar, Amandeep , Sheth, Udit , Coyne, Alyssa N. , Punathil, Ritika , Kang, Bong Gu , Dasovich, Morgan , Veire, Austin M. , Hernandez, Mariely DeJesus, Liu, Shuaichen , Shi, Zheng , Dafinca, Ruxandra , Talbot, Kevin , Zhang, Yong‐Jie , Petrucelli, Leonard , Blitterswijk, Marka van , Guo, Lin , Dawson, Ted M. , Veire, Austin , DeJesus Hernandez, Mariely, Fouquerel, Elise , Talbot, Kevin , Kam, Tae-In , Zhang, Yong-Jie , Dickson, Dennis W , Petrucelli, Leonard , van Blitterswijk, Marka , Guo, Lin , Dawson, Ted M , Dawson, Valina L , Leung, Anthony K L , Lloyd, Thomas E , Gendron, Tania F , Rothstein, Jeffrey D , Zhang, Ke , Coyne, Alyssa N , Sheth, Udit , Liu, Shuaichen, Kam, Tae‐In , Dickson, Dennis W. , Dawson, Valina L. , Gendron, Tania F. , Rothstein, Jeffrey D. , Zhang, Ke

Science Translational Medicine | September 14, 2022 | Volume: 14 | Issue: 662 | Pages: No page available

10.1126/scitranslmed.abq3215 Get It

Arginine-rich dipeptide repeat proteins (R-DPRs), abnormal translational products of a GGGGCC hexanucleotide repeat expansion in C9ORF72 , play a critical role in C9ORF72 -related amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), the most common genetic form of the disorders (c9ALS/FTD). R-DPRs form liquid condensates in vitro, induce stress granule formation in cultured cells, aggregate, and sometimes coaggregate with TDP-43 in postmortem tissue from patients with c9ALS/FTD. However, how these processes are regulated is unclear. Here, we show that loss of poly(ADP-ribose) (PAR) suppresses neurodegeneration in c9ALS/FTD fly models and neurons differentiated from patient-derived induced pluripotent stem cells. Mechanistically, PAR induces R-DPR condensation and promotes R-DPR–induced stress granule formation and TDP-43 aggregation. Moreover, PAR associates with insoluble R-DPR and TDP-43 in postmortem tissue from patients. These findings identified PAR as a promoter of R-DPR toxicity and thus a potential target for treating c9ALS/FTD.
Ribonuclease recruitment using a small molecule reduced c9ALS/FTD r(G 4 C 2 ) repeat expansion in vitro and in vivo ALS models
Bush, Jessica A. , Aikawa, Haruo , Fuerst, Rita, Li, Yue , Ursu, Andrei , Meyer, Samantha M. , Benhamou, Raphael I. , Chen, Jonathan L. , Khan, Tanya , Wagner-Griffin, Sarah , Meter, Montina J. Van , Tong, Yuquan , Olafson, Hailey, McKee, Kendra , Childs‐Disney, Jessica L. , Zhang, Yong‐Jie , Wang, Eric T. , Wang, Kye Won , Petrucelli, Leonard , Van Meter, Montina J , McKee, Kendra K , Gendron, Tania F , Zhang, Yong-Jie , Coyne, Alyssa N , Wang, Eric T , Wang, Kye Won , Petrucelli, Leonard , Rothstein, Jeffrey D , Disney, Matthew D , Benhamou, Raphael I , Aikawa, Haruo , Gendron, Tania F. , Coyne, Alyssa N. , Yildirim, Ilyas , Rothstein, Jeffrey D. , Disney, Matthew D.

Science Translational Medicine | October 27, 2021 | Volume: 13 | Issue: 617 | Pages: No page available

10.1126/scitranslmed.abd5991 Get It

Small-molecule recruitment of an endogenous nuclease rescues pathologies associated with c9ALS/FTD in vivo by targeting an RNA repeat expansion.
Nuclear accumulation of CHMP7 initiates nuclear pore complex injury and subsequent TDP-43 dysfunction in sporadic and familial ALS
Coyne, Alyssa N. , Baskerville, Victoria, Zaepfel, Benjamin L. , Dickson, Dennis W. , Rigo, Frank , Bennett, Frank , Lusk, C. Patrick , Rothstein, Jeffrey D. , Dickson, Dennis W , Coyne, Alyssa N , Rothstein, Jeffrey D

Science Translational Medicine | July 28, 2021 | Volume: 13 | Issue: 604 | Pages: No page available

10.1126/scitranslmed.abe1923 Get It

Nuclear accumulation of CHMP7 leads to multiple cellular pathologies that can be mitigated via CHMP7 ASOs in familial and sporadic ALS iPSNs.