Article
Biochemistry & Molecular Biology
Restuadi Restuadi, Fleur C. Garton, Beben Benyamin, Tian Lin, Kelly L. Williams, Anna Vinkhuyzen, Wouter van Rheenen, Zhihong Zhu, Nigel G. Laing, Karen A. Mather, Perminder S. Sachdev, Shyuan T. Ngo, Frederik J. Steyn, Leanne Wallace, Anjali K. Henders, Peter M. Visscher, Merrilee Needham, Susan Mathers, Garth Nicholson, Dominic B. Rowe, Robert D. Henderson, Pamela A. McCombe, Roger Pamphlett, Ian P. Blair, Naomi R. Wray, Allan F. McRae
Summary: Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disease with genetic and non-genetic risk factors. Recent studies have found genetic correlations between ALS and traits such as schizophrenia, cognitive performance, and educational attainment, and using multi-trait genetic predictors can improve prediction accuracy in case-control studies.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Cell Biology
Badwi B. Boumelhem, Chelsea Pilgrim, Vincent E. Zwicker, Jacek L. Kolanowski, Jia Hao Yeo, Katrina A. Jolliffe, Elizabeth J. New, Margot L. Day, Stephen J. Assinder, Stuart T. Fraser
Summary: This article describes a simple and inexpensive method to determine lipid content in cells, and highlights the differences in lipid biology between cell types using imaging and flow cytometry.
JOURNAL OF CELL SCIENCE
(2022)
Review
Neurosciences
Fabia Filipello, Claire Goldsbury, Shih Feng You, Alberto Locca, Celeste M. Karch, Laura Piccio
Summary: This article reviews the role of TREM2, focusing on its potential functions as a biomarker in neurological disorders and as a potential therapeutic target for CNS diseases.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Biology
Kimberly J. Morgan, Karen Doggett, Fansuo Geng, Stephen Mieruszynski, Lachlan Whitehead, Kelly A. Smith, Benjamin M. Hogan, Cas Simons, Gregory J. Baillie, Ramyar Molania, Anthony T. Papenfuss, Thomas E. Hall, Elke A. Ober, Didier Y. R. Stainier, Zhiyuan Gong, Joan K. Heath
Summary: Reducing ahctf1 gene dosage significantly decreases liver volume in a hepatocellular carcinoma model and impairs nuclear pore formation, mitotic spindle assembly, and chromosome segregation in the context of cancer, leading to DNA damage and cell death.
Article
Cell Biology
Yeping Wu, Ye-Wheen Lim, David A. Stroud, Nick Martel, Thomas E. Hall, Harriet P. Lo, Charles Ferguson, Michael T. Ryan, Kerrie-Ann McMahon, Robert G. Parton
Summary: Using quantitative whole-cell proteomics, researchers found that the oxidative stress response is the major pathway dysregulated in cells lacking the caveola structural protein CAVIN1. CAVIN1 deletion compromised sensitivity to oxidative stress and wound-induced reactive oxygen species accumulation, affecting regeneration. Oxidative stress triggered lipid peroxidation and caveolar disassembly, allowing release of CAVIN1 and direct interaction with NRF2, resulting in NRF2 degradation and resistance to lipid-peroxidation-induced ferroptosis in CAVIN1-null cells.
DEVELOPMENTAL CELL
(2023)
Article
Biochemistry & Molecular Biology
Natalie E. Farrawell, Monique Bax, Luke McAlary, Jessie McKenna, Simon Maksour, Dzung Do-Ha, Stephanie L. Rayner, Ian P. Blair, Roger S. Chung, Justin J. Yerbury, Lezanne Ooi, Darren N. Saunders
Summary: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are fatal neurodegenerative disorders characterized by the accumulation of ubiquitinated protein inclusions in motor neurons. A pathogenic variant in the CCNF gene was found to disrupt ubiquitin homeostasis, leading to dysfunction in the ubiquitin-proteasome system (UPS) and contributing to the development of CCNF-associated ALS/FTD.
HUMAN MOLECULAR GENETICS
(2023)
Article
Neurosciences
Jennilee M. Davidson, Sharlynn S. L. Wu, Stephanie L. Rayner, Flora Cheng, Kimberley Duncan, Carlo Russo, Michelle Newbery, Kunjie Ding, Natalie M. Scherer, Rachelle Balez, Alberto Garcia-Redondo, Alberto Rabano, Livia Rosa-Fernandes, Lezanne Ooi, Kelly L. Williams, Marco Morsch, Ian P. Blair, Antonio Di Ieva, Shu Yang, Roger S. Chung, Albert Lee
Summary: This study reveals the role of cyclin F in regulating substrate solubility and its contribution to the pathogenesis of ALS and FTD. The ALS and FTD-associated protein p62 is identified as a substrate of cyclin F, and its aggregation is promoted by cyclin F expression. Mutations in cyclin F result in dysregulated p62 solubility and formation of p62 foci, which are associated with ALS and FTD pathogenesis.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Neurosciences
Hasinika K. A. H. Gamage, Katherine J. Robinson, Luan Luu, Ian T. Paulsen, Angela S. Laird
Summary: Emerging evidence suggests bidirectional interactions between the central nervous system and gut microbiota in neurodegenerative diseases, but the role of gut microbes in spinocerebellar ataxia, specifically Machado Joseph disease (MJD), is unknown. This study found sex-specific effects in MJD development and differences in gut microbiota composition between MJD and wild-type mice. The pre-symptomatic microbial changes correlated with the severity of neurological impairments, indicating a potential new target for treating this currently untreatable disease.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Clinical Neurology
Allison A. Dilliott, Ahmad Al Nasser, Marwa Elnagheeb, Jennifer Fifita, Lyndal Henden, Ingrid M. Keseler, Steven Lenz, Heather Marriott, Emily Mccann, Maysen Mesaros, Sarah Opie-Martin, Emma Owens, Brooke Palus, Justyne Ross, Zhanjun Wang, Hannah White, Ammar Al-Chalabi, Peter M. Andersen, Michael Benatar, Ian Blair, Johnathan Cooper-Knock, Elizabeth A. Harrington, Jeannine Heckmann, John Landers, Cristiane Moreno, Melissa Nel, Evadnie Rampersaud, Jennifer Roggenbuck, Guy Rouleau, Bryan Traynor, Marka Van Blitterswijk, Wouter Van Rheenen, Jan Veldink, Jochen Weishaupt, Luke Drury, Matthew B. Harms, Sali M. K. Farhan
Summary: The establishment of the Clinical Genome Resource (ClinGen) amyotrophic lateral sclerosis (ALS) spectrum disorders Gene Curation Expert Panel (GCEP) aimed to evaluate the strength of evidence for genes associated with ALS. This study assessed the heterogeneity in clinical genetic testing panels for ALS and found variability in the genes included, suggesting the need for consensus on gene inclusions to improve diagnostic yields and reduce missed diagnoses. The findings highlight the importance of standardized guidance for laboratories and better application of genetic testing for ALS patients and their families.
AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
(2023)
Article
Multidisciplinary Sciences
Lyndal Henden, Liam G. Fearnley, Natalie Grima, Emily P. McCann, Carol Dobson-Stone, Lauren Fitzpatrick, Kathryn Friend, Lynne Hobson, Sandrine Chan Moi Fat, Dominic B. Rowe, Susan D'Silva, John B. Kwok, Glenda M. Halliday, Matthew C. Kiernan, Srestha Mazumder, Hannah C. Timmins, Margaret Zoing, Roger Pamphlett, Lorel Adams, Melanie Bahlo, Ian P. Blair, Kelly L. Williams
Summary: In this study, we analyzed whole-genome sequencing data from 608 patients with sporadic ALS, 68 patients with sporadic FTD, and 4703 matched controls using three tools. We found that 17.6% of clinically diagnosed ALS and FTD cases had expanded STR alleles reported to be pathogenic or intermediate for other neurodegenerative diseases, providing evidence for their contribution to the development of these diseases. We also identified multiple disease-relevant STR expansions associated with neurodegenerative diseases, highlighting the clinical and pathological pleiotropy of neurodegenerative disease genes and their importance in ALS and FTD.
Article
Biochemistry & Molecular Biology
Thomas E. Hall, Nicholas Ariotti, Harriet P. Lo, James Rae, Charles Ferguson, Nick Martel, Ye-Wheen Lim, Jean Giacomotto, Robert G. Parton
Summary: Plasma membrane rupture can lead to cell death. This study uses an active trapping model to investigate the structural changes of sarcolemma, showing the essential role of caveolae in maintaining sarcolemmal integrity and quantifying the contribution of caveolar-derived membrane to surface expansion.
Article
Clinical Neurology
Natalie Grima, Sidong Liu, Dean Southwood, Lyndal Henden, Andrew Smith, Albert Lee, Dominic B. Rowe, Susan D'Silva, Ian P. Blair, Kelly L. Williams
Summary: Peripheral blood RNA-seq can identify diagnostic biomarkers in ALS patients and distinguish molecular subtypes, but its prognostic value needs further investigation.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2023)
Article
Clinical Neurology
Emily P. McCann, Natalie Grima, Jennifer A. Fifita, Sandrine Chan Moi Fat, Klaus Lehnert, Lyndal Henden, Ian P. Blair, Kelly L. Williams
Summary: This study provides a comprehensive catalog of genetic variations in amyotrophic lateral sclerosis (ALS) and analyzes the characteristics of these variations and their contribution to the disease. The findings suggest that the variations found in sporadic ALS cases are less severe than those observed in familial ALS.
JOURNAL OF NEUROMUSCULAR DISEASES
(2023)