Article
Cell Biology
Cristina Marisol Castillo Bautista, Kristin Eismann, Marc Gentzel, Silvia Pelucchi, Jerome Mertens, Hannah E. Walters, Maximina H. Yun, Jared Sterneckert
Summary: Aging disrupts protein homeostasis and contributes to various diseases, including ALS. Repressing autophagy is a strategy to restore protein homeostasis and protect neurons. A study found that obatoclax, a small molecule BH3 mimetic, can disrupt the interaction between BECN1 and BCL2, reducing FUS levels and improving protein homeostasis to rescue neurons. Obatoclax has potential as a therapeutic for ALS and other age-related disorders linked to protein homeostasis defects.
Article
Neurosciences
Luigi Fiondella, Francesco Cavallieri, Elena Canali, Maria Paola Cabboi, Alessandro Marti, Francesca Sireci, Alena Fiocchi, Gloria Montanari, Sara Montepietra, Franco Valzania
Summary: The simultaneous occurrence of relapsing remitting multiple sclerosis (RRMS) and amyotrophic lateral sclerosis (ALS) is rare. This case report describes a 49-year-old woman with a history of RRMS who developed progressive weakness in her left arm. The patient's father had ALS, and her paternal uncle had Parkinson's disease. Imaging and electromyography confirmed the co-occurrence of RRMS and ALS in this patient.
Article
Biochemistry & Molecular Biology
Byung Jo Choi, Kang Ho Park, Min Hee Park, Eric Jinsheng Huang, Seung Hyun Kim, Jae-sung Bae, Hee Kyung Jin
Summary: Studies have shown that increased activity of acid sphingomyelinase (ASM) is observed in both ALS patients and mouse models. Genetic inhibition of ASM can improve symptoms and reduce spinal neuronal loss in an ALS mouse model. These findings suggest that ASM may be an effective therapeutic target for ALS.
Article
Medicine, General & Internal
Peishan Wang, Qiao Wei, Hongfu Li, Zhi-Ying Wu
Summary: This study screened for mutations in JALS patients and found a novel SPTLC1 mutation. Compared to patients with FUS mutations, JALS patients with SPTLC1 mutations had an earlier age of onset, longer disease duration, and no bulbar symptoms.
CHINESE MEDICAL JOURNAL
(2023)
Review
Biochemistry & Molecular Biology
Sophie Layalle, Laetitia They, Sarah Ourghani, Cedric Raoul, Laurent Soustelle
Summary: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the degeneration of motoneurons. Fruit flies have emerged as a versatile model for studying ALS, providing insights into cellular mechanisms and potential therapeutic targets for future treatments. Research on fruit fly ALS models has revealed novel pathogenic mechanisms and identified disease-modifying genes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Clinical Neurology
Xuan Chen, Jing Luo, Wei Zheng, Qinlian Huang, Chao Du, Huan Yuan, Fei Xiao
Summary: This article presents the clinical characteristics of a young female ALS patient with a fused in sarcoma (FUS) gene mutation and notable hyperhidrosis. The study found that autonomic nervous symptoms in ALS were associated with FUS mutation, emphasizing the importance of early diagnosis and timely treatment intervention to enhance patient prognosis.
NEUROLOGICAL SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Katarina Maksimovic, Mohieldin Youssef, Justin You, Hoon-Ki Sung, Jeehye Park
Summary: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects motor neurons, leading to muscle weakness, paralysis, and eventual death. Recent research has shown that ALS is not only limited to motor neurons, but also involves systemic metabolic dysfunction. This review examines the metabolic dysfunction in ALS at various levels, including muscle tissue, adipose tissue, liver, pancreas, and the central nervous system. It also discusses the future prospects of metabolic research in ALS and potential treatment options.
Article
Genetics & Heredity
Tanya Lehky, Christopher Grunseich
Summary: Juvenile amyotrophic lateral sclerosis (JALS) is a rare group of motor neuron disorders with gene association in 40% of cases, defined by onset before age 25. The most common gene mutations associated with JALS are FUS, SETX, and ALS2, with familial cases mostly inherited in an autosomal recessive pattern.
Article
Clinical Neurology
Jing Ma, Xiaomin Pang, Shan Huang, Jing Zhang, Juan Wang, Rongjuan Zhao, Xueli Chang, Junhong Guo, Wei Zhang
Summary: The study aimed to investigate genetic characteristics in Chinese patients with familial or young-onset ALS, identifying two novel mutations. Patients with familial or young-onset ALS often carried related gene mutations, suggesting routine genetic sequencing should be performed.
NEUROLOGICAL SCIENCES
(2022)
Article
Multidisciplinary Sciences
Jelena Scekic-Zahirovic, Inmaculada Sanjuan-Ruiz, Vanessa Kan, Salim Megat, Pierre De Rossi, Stephane Dieterle, Raphaelle Cassel, Marguerite Jamet, Pascal Kessler, Diana Wiesner, Laura Tzeplaeff, Valerie Demais, Sonu Sahadevan, Katharina M. Hembach, Hans-Peter Muller, Gina Picchiarelli, Nibha Mishra, Stefano Antonucci, Sylvie Dirrig-Grosch, Jan Kassubek, Volker Rasche, Albert Ludolph, Anne-Laurence Boutillier, Francesco Roselli, Magdalini Polymenidou, Clotilde Lagier-Tourenne, Sabine Liebscher, Luc Dupuis
Summary: Mutations in the RNA binding protein FUS are associated with ALS. Here the authors show that in FUS knock-in mice there is a progressive increase in neuronal activity in the frontal cortex which is associated with altered synaptic gene expression.
NATURE COMMUNICATIONS
(2021)
Article
Geriatrics & Gerontology
Suzanna Edgar, Melina Ellis, Nur Adilah Abdul-Aziz, Khean-Jin Goh, Nortina Shahrizaila, Marina L. Kennerson, Azlina Ahmad-Annuar
Summary: This study identified mutations in SOD1 and C9orf72 genes in a multi-ethnic Malaysian ALS cohort, with a mutation frequency of 5.9%. No mutations were found in FUS and TARDBP genes. Further investigation is needed to uncover novel genes and disease pathways in ALS.
NEUROBIOLOGY OF AGING
(2021)
Review
Cell Biology
Jiantao Zhao, Xuemei Wang, Zijun Huo, Yanchun Chen, Jinmeng Liu, Zhenhan Zhao, Fandi Meng, Qi Su, Weiwei Bao, Lingyun Zhang, Shuang Wen, Xin Wang, Huancai Liu, Shuanhu Zhou
Summary: Amyotrophic lateral sclerosis (ALS) is a rapidly progressing and highly fatal neurodegenerative disease. Mitochondrial dysfunction is believed to be a key contributing factor to the pathogenesis of ALS. Stable mitochondrial function is crucial for normal neuron function, and dysfunction can lead to cellular pathological changes and play an important role in the progression of ALS.
Article
Biochemistry & Molecular Biology
Thibaut Burg, Elisabeth Rossaert, Matthieu Moisse, Philip Van Damme, Ludo Van den Bosch
Summary: Amyotrophic lateral sclerosis (ALS) is an incurable and fatal neurodegenerative disorder of the motor system, with defects in metabolism contributing significantly to disease progression. Inhibition of histone deacetylase (HDAC) has been shown to restore metabolic alterations and mitigate lipid homeostasis defects in ALS, suggesting a potential new therapeutic strategy for modulating lipid metabolism in ALS and potentially other neurodegenerative diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Clinical Neurology
Hiroyuki Honda, Motoi Yoshimura, Hajime Arahata, Kaoru Yagita, Shoko Sadashima, Hideomi Hamasaki, Masahiro Shijo, Sachiko Koyama, Hideko Noguchi, Naokazu Sasagasako
Summary: FUS mutations play a significant role in ALS-FUS and colocalize with other hnRNPs such as TDP43, PCBP2, and PCBP1, suggesting impaired RNA metabolism.
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2023)
Article
Oncology
Qinming Zhou, Lu He, Jin Hu, Yining Gao, Dingding Shen, You Ni, Yuening Qin, Huafeng Liang, Jun Liu, Weidong Le, Sheng Chen
Summary: The role of CORO1A in ALS pathogenesis was discovered, potentially affecting the disease onset and progression by blocking autophagic flux. Therefore, CORO1A might be a potential biomarker and therapeutic target for ALS.
FRONTIERS OF MEDICINE
(2022)