Article
Biochemistry & Molecular Biology
Ligia Fao, Patricia Coelho, Luis Duarte, Rita Vilaca, Michael R. Hayden, Sandra I. Mota, Ana Cristina Rego
Summary: This study demonstrates that c-Src/Fyn proteins play an important role in controlling mitochondrial function and redox regulation in Huntington's disease (HD). Restoring c-Src/Fyn levels in HD improves mitochondrial morphology and function, reducing the levels of oxidant species and cell death. These findings suggest that c-Src/Fyn could be a potential therapeutic target for HD.
ANTIOXIDANTS & REDOX SIGNALING
(2023)
Article
Cell Biology
Shao-Ming Wang, Hsiang-En Wu, Yuko Yasui, Michal Geva, Michael Hayden, Tangui Maurice, Mauro Cozzolino, Tsung-Ping Su
Summary: Autophagy is a crucial cellular process with implications in various diseases. In this study, researchers discovered that the molecular chaperone SIGMAR1 is involved in the transport of TFEB into the nucleus by chaperoning the NP protein POM121, which is responsible for recruiting KPNB1. The disruption of this process in ALS-FTD patients with the C9orf72 subtype leads to impaired autophagy. However, overexpression of SIGMAR1 or POM121, as well as treatment with pridopidine, a SIGMAR1 agonist, can rescue these deficits, suggesting their potential therapeutic use.
Article
Oncology
Morgan E. Rook, Amber L. Southwell
Summary: Huntington disease is a fatal neurodegenerative disorder caused by an inherited mutation in the huntingtin gene. Lowering mutant huntingtin protein (HTT) has shown promise as a potential disease-modifying treatment. Antisense oligonucleotides (ASOs) that target HTT transcripts offer a suitable approach, and they have gained attention as a therapeutic option for Huntington disease. However, recent clinical trials assessing two types of ASOs for Huntington disease were halted early.
Article
Astronomy & Astrophysics
Govind Nandakumar, Michael R. Hayden, Sanjib Sharma, Sven Buder, Martin Asplund, Joss Bland-Hawthorn, Gayandhi M. De Silva, Valentina D'Orazi, Ken C. Freeman, Janez Kos, Geraint F. Lewis, Sarah L. Martell, Katharine J. Schlesinger, Jane Lin, Jeffrey D. Simpson, Daniel B. Zucker, Tomaz Zwitter, Thomas Nordlander, Luca Casagrande, Karin Lind, Klemen Cotar, Dennis Stello, Robert A. Wittenmyer, Thor Tepper-Garcia
Summary: APOGEE and GALAH are two high-resolution multi-object spectroscopic surveys that provide fundamental stellar parameters and multiple elemental abundance estimates for about half a million stars in the Milky Way. However, due to the different observational wavelengths and data reduction methods used, there are significant differences and trends in stellar parameters and abundances between the two surveys. To address this, the Cannon data-driven method is utilized to create calibrated catalogues for each survey. High precision in metallicity and alpha abundances is achieved through repeat observations and validation. The final catalogues are cross-matched with the Gaia EDR3 catalogue to enable detailed chemo-dynamic studies of the Milky Way.
MONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY
(2022)
Article
Neurosciences
Nicholas S. Caron, Raul Banos, Amirah E. Aly, Yuanyun Xie, Seunghyun Ko, Nalini Potluri, Christine Anderson, Hailey Findlay Black, Lisa M. Anderson, Benjamin Gordon, Amber L. Southwell, Michael R. Hayden
Summary: Huntington's disease is a neurodegenerative disease caused by a trinucleotide repeat expansion in the HTT gene. Therapies that lower mutant huntingtin (mHTT) in the central nervous system (CNS) have shown promise, and quantitation of mHTT in the cerebrospinal fluid (CSF) is being used as a biomarker. This study demonstrates that the striatum contributes significantly to CSF mHTT and suggests that CSF mHTT may be a biomarker for therapies targeting mHTT in the striatum.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Astronomy & Astrophysics
Yaguang Li, Timothy R. Bedding, Simon J. Murphy, Dennis Stello, Yifan Chen, Daniel Huber, Meridith Joyce, Dion Marks, Xianfei Zhang, Shaolan Bi, Isabel L. Colman, Michael R. Hayden, Daniel R. Hey, Gang Li, Benjamin T. Montet, Sanjib Sharma, Yaqian Wu
Summary: A star expands into a red giant when all the hydrogen in its core has fused into helium. In binary systems, the envelope of the star can overflow onto its companion or be ejected into space, potentially forming a subdwarf B star. By observing thousands of helium-burning red giants, scientists have identified two classes of stars that have undergone significant mass loss, possibly due to stripping in binary interactions.
Article
Biochemistry & Molecular Biology
Carla Lopes, I. Luisa Ferreira, Carina Maranga, Margarida Beatriz, Sandra I. Mota, Jose Sereno, Joao Castelhano, Antero Abrunhosa, Francisco Oliveira, Maura De Rosa, Michael Hayden, Mario N. Laco, Cristina Januario, Miguel Castelo Branco, A. Cristina Rego
Summary: Deficits in mitochondrial function and redox deregulation occur in early stages of Huntington's disease and can progress with disease manifestation.
Article
Biology
Pawel Joachimiak, Adam Ciesiolka, Emilia Kozlowska, Pawel M. Switonski, Grzegorz Figura, Agata Ciolak, Grazyna Adamek, Magdalena Surdyka, Zaneta Kalinowska-Poska, Maciej Figiel, Nicholas S. S. Caron, Michael R. R. Hayden, Agnieszka Fiszer
Summary: This study used SNP variants to quantitatively determine the allele-specific expression levels in patient-derived cell lines for spinocerebellar ataxia type 3 (SCA3) and Huntington's disease (HD). They found differences in allele expression levels and developed a reliable and quantitative method using SNP-based droplet digital PCR (ddPCR) to analyze low abundant transcripts. This allele-selective approach provides insights into allele-related mechanisms and can improve understanding of polyglutamine diseases.
Article
Physiology
Fanny L. Lemarie, Shaun S. Sanders, Yen Nguyen, Dale D. O. Martin, Michael R. Hayden
Summary: Huntington's disease is a neurodegenerative disorder caused by CAG repeat expansion in the HTT gene. We found that huntingtin protein can be palmitoylated at cysteine 214, and proteolytic cleavage at aspartate 552 leads to myristoylation at glycine 553. Blocking caspase cleavage at aspartate 586 increases myristoylation of huntingtin and promotes the interaction between C-terminal and N-terminal fragments.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Neurosciences
Laura Lynn Chan, Austin Hill, Ge Lu, Jeremy Van Raamsdonk, Randy Gascoyne, Michael R. Hayden, Blair R. Leavitt
Summary: There is no significant effect of mutant or overexpression of huntingtin protein on overall survival in mouse models of cancer, which contradicts the hypothesis that mutant huntingtin expression is protective against cancer.
JOURNAL OF HUNTINGTONS DISEASE
(2022)
Article
Neurosciences
James P. Mackay, Amy I. Smith-Dijak, Ellen T. Koch, Peng Zhang, Evan Fung, Wissam B. Nassrallah, Caodu Buren, Mandi Schmidt, Michael R. Hayden, Lynn A. Raymond
Summary: Miniature neurotransmission is increased in the Huntington disease (HD) model, associated with abnormal endoplasmic reticulum (ER) calcium handling. These abnormalities influence neurotransmission indirectly, without direct ER calcium release into the cytoplasm. However, in cortical cultures and brain slices, there are no significant differences in calcium release between the HD-model neurons and wild-type cells.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Clinical Neurology
Borje Darpo, Michal Geva, Georg Ferber, Yigal Paul Goldberg, Andres Cruz-Herranz, Munish Mehra, Richard Kovacs, Michael R. Hayden
Summary: Pridopidine, a selective sigma-1 receptor agonist, shows a favorable cardiac safety profile at the therapeutic dose of 45 mg bid, with no clinically relevant effect on the QT interval.
NEUROLOGY AND THERAPY
(2023)
Article
Biotechnology & Applied Microbiology
Neel Mehta, Renald Gilbert, Parminder S. Chahal, Maria J. Moreno, Nasha Nassoury, Nathalie Coulombe, Viktoria Lytvyn, Mario Mercier, Dorothy Fatehi, Wendy Lin, Emily M. Harvey, Lin-Hua Zhang, Nazila Nazemi-Moghaddam, Seyyed Mehdy Elahi, Colin J. D. Ross, Danica B. Stanimirovic, Michael R. Hayden
Summary: This study aimed to develop a more efficacious AAV gene therapy vector for the treatment of LPLD. The researchers identified AAV8 pVR59 as a superior vector compared to AAV1 (Glybera), with significantly better therapeutic effects at lower doses. AAV8 pVR59 treatment led to long-term correction of LPLD and improvement in pathology.
HUMAN GENE THERAPY
(2023)
Article
Biotechnology & Applied Microbiology
Fabio Duarte, Gabriel Vachey, Nicholas S. Caron, Melanie Sipion, Maria Rey, Anselme L. Perrier, Michael R. Hayden, Nicole Deglon
Summary: Huntington's disease is a fatal neurodegenerative disorder that can be treated by inactivating the mutated HTT gene. One approach to selectively inactivate the mutant allele is by using the CRISPR/Cas9 system to remove the first exon of the mutated HTT. However, the frequency of deletion events is still uncertain.
HUMAN GENE THERAPY
(2023)
Meeting Abstract
Clinical Neurology
Libo Yu-Taeger, Arianna Novati, Jonasz Jeremiasz Weber, Elisabeth Singer-Mikosch, Ann-Sophie Pabst, Carsten Saft, Jennifer Koenig, Gisa Ellrichmann, Taneli Heikkinen, Mahmoud A. Pouladi, Olaf Riess, Huu Phuc Nguyen
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)