Article
Neurosciences
Rebecca Stevenson, Evgeniia Samokhina, Armaan Mangat, Ilaria Rossetti, Sushmitha S. Purushotham, Chandra S. Malladi, John W. Morley, Yossi Buskila
Summary: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the progressive loss of motor neurons. Recent studies have shown that astrocytes, a type of glial cells, also contribute to the onset and progression of ALS. This study investigates the role of astrocytes in maintaining K+ homeostasis in the brain and demonstrates region-specific alterations in K+ clearance rate in an ALS mouse model. The findings suggest that impaired astrocytic function may contribute to the vulnerability of motor neurons in ALS.
Article
Biochemistry & Molecular Biology
Niccolo Candelise, Illari Salvatori, Silvia Scaricamazza, Valentina Nesci, Henri Zenuni, Alberto Ferri, Cristiana Valle
Summary: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of upper and lower motor neurons. Despite efforts to understand its pathogenesis, ALS remains obscure and lacks effective therapies. Recent studies have highlighted the central role of mitochondrial dysfunction in ALS, leading to impaired energy metabolism.
Review
Pharmacology & Pharmacy
Yutaka Nakagawa, Shizuo Yamada
Summary: ALS is a progressive neurodegenerative disorder characterized by motor dysfunctions resulting from the loss of upper and lower motor neurons. The imbalance of metals and mitochondrial dysfunction may play a key role in the initiation and progression of ALS symptoms, affecting both motor and extra-motor functions.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Clinical Neurology
Arpan R. Mehta, Jenna M. Gregory, Owen Dando, Roderick N. Carter, Karen Burr, Jyoti Nanda, David Story, Karina McDade, Colin Smith, Nicholas M. Morton, Don J. Mahad, Giles E. Hardingham, Siddharthan Chandran, Bhuvaneish T. Selvaraj
Summary: The study found that axonal dysfunction in C9orf72-ALS patients is associated with shorter axons, impaired mitochondrial transport, and altered mitochondrial bioenergetics, indicating that mitochondrial dysfunction is a key factor in axonal dysfunction. Increasing mitochondrial biogenesis through genetic manipulation can correct the bioenergetic deficit and rescue axonal length and transport phenotypes.
ACTA NEUROPATHOLOGICA
(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.
Review
Biochemistry & Molecular Biology
Milena Jankovic, Ivana Novakovic, Phepy Gamil Anwar Dawod, Ayman Gamil Anwar Dawod, Aleksandra Drinic, Fayda I. Abdel Motaleb, Sinisa Ducic, Dejan Nikolic
Summary: ALS is a neurodegenerative motor neuron disorder with a significant genetic component, involving RNA processing, protein aggregation, oxidative stress, glutamate excitotoxicity, and inflammation. Mitochondrial dysfunction is a major contributor to disease onset and progression, highlighting the need for a broad perspective in understanding overlapping pathophysiological pathways and exploring potential therapies targeting mitochondrial dysfunction.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Food Science & Technology
Salvatore D'Antona, Martina Caramenti, Danilo Porro, Isabella Castiglioni, Claudia Cava
Summary: Amyotrophic lateral sclerosis (ALS) is a fatal disease linked to motor neurons degeneration, with diet components like oxidative stress potentially influencing its onset. Some diets with antioxidant and anti-inflammatory properties may reduce the risk of ALS, but current data remains controversial.
Article
Medicine, Research & Experimental
Xiao Li, Chongyang Chen, Xu Zhan, Binyao Li, Zaijun Zhang, Shupeng Li, Yongmei Xie, Xiangrong Song, Yuanyuan Shen, Jianjun Liu, Ping Liu, Gong-Ping Liu, Xifei Yang
Summary: The study showed that treatment with R13 significantly slowed the abnormal motor performance of ALS mice, reduced the proliferation of microglia and astrocytes, promoted mitochondrial biogenesis, and increased the survival rate of worms expressing G93A SOD1.
Review
Biochemistry & Molecular Biology
Elena Obrador, Rosario Salvador-Palmer, Rafael Lopez-Blanch, Ryan W. Dellinger, Jose M. Estrela
Summary: ALS is a degenerative disease with no cure or proven therapy. While some drugs have been approved for treatment, there has been no significant breakthrough in the field.
Article
Cell Biology
Seung-Hye Choi, Ali Yousefian-Jazi, Seung Jae Hyeon, Phuong Thi Thanh Nguyen, Jiyeon Chu, Sojung Kim, Suhyun Kim, Hannah L. Ryu, Neil W. Kowall, Hoon Ryu, Junghee Lee
Summary: In this study, researchers found that modulating the activity of LSD1 can improve the neuropathology of ALS mice, delay disease onset, and extend lifespan, potentially serving as an effective therapeutic strategy for treating ALS.
JOURNAL OF BIOMEDICAL SCIENCE
(2022)
Article
Clinical Neurology
Yuichi Nishikawa, Ales Holobar, Kohei Watanabe, Tetsuya Takahashi, Hiroki Ueno, Noriaki Maeda, Hirofumi Maruyama, Shinobu Tanaka, Allison S. Hyngstrom
Summary: This study detected specific motor unit (MU) abnormalities in people with amyotrophic lateral sclerosis (ALS) using high-density surface electromyography (HD-SEMG). The results showed that ALS patients had abnormal MU firing behavior compared to controls, and these abnormalities were correlated with disease severity.
CLINICAL NEUROPHYSIOLOGY
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Giorgio Conte, Valeria Elisa Contarino, Silvia Casale, Claudia Morelli, Sara Sbaraini, Elisa Scola, Francesca Trogu, Silvia Siggillino, Claudia Maria Cinnante, Luca Caschera, Francesco Maria Lo Russo, Fabio Maria Triulzi, Vincenzo Silani
Summary: The study aimed to investigate whether magnetic susceptibility varies according to ALS phenotypes based on UMN/LMN sign predominance. Results showed significant differences in susceptibility properties of the precentral cortex among different clinical ALS phenotypes. Combined MRI-histopathology investigations are needed to confirm the evidence of iron overload in UMN-ALS unlike in LMN-ALS.
EUROPEAN RADIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Giada Zanini, Valentina Selleri, Milena Nasi, Anna De Gaetano, Ilaria Martinelli, Giulia Gianferrari, Francesco Demetrio Lofaro, Federica Boraldi, Jessica Mandrioli, Marcello Pinti
Summary: This study reports the clinical and biological features of an ALS patient with pA382T mutation in TPD-43 protein. The mutation leads to significant alterations in neuronal proteome, particularly impacting mitochondrial metabolic pathways and the endoplasmic reticulum. The findings suggest that mitochondrial dysfunction and misplacement of mitochondrial DNA may be mechanisms contributing to ALS caused by this mutation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Patrizia M. Maier, Deetje Iggena, Thomas Meyer, Carsten Finke, Christoph J. Ploner
Summary: This study found no evidence of hippocampal dysfunction in non-demented ALS patients, suggesting that the cognitive phenotype of ALS may relate to distinct disease subtypes rather than being a variable expression of the same underlying condition.
JOURNAL OF NEUROLOGY
(2023)
Review
Clinical Neurology
Georgiana Soares Leandro, Mario Emilio Teixeira Dourado Junior, Glauciane Costa Santana, Luan Samy Xavier Dantas
Summary: The main coping strategy used by ALS patients is seeking social support, while Confrontive coping and Distancing are less commonly mentioned. The coping strategies of ALS patients do not seem to focus on emotions or stress-triggering problems, and age and gender do not modify the chosen strategy.
JOURNAL OF NEUROLOGY
(2022)
Article
Neurosciences
Emiliano Trias, Mariangeles Kovacs, Peter H. King, Ying Si, Yuri Kwon, Valentina Varela, Sofia Ibarburu, Ivan C. Moura, Olivier Hermine, Joseph S. Beckman, Luis Barbeito
Article
Biochemistry & Molecular Biology
Mandi Gandelman, Warunee Dansithong, Karla P. Figueroa, Sharan Paul, Daniel R. Scoles, Stefan M. Pulst
CELL DEATH AND DIFFERENTIATION
(2020)
Article
Biochemistry & Molecular Biology
Daniel R. Scoles, Warunee Dansithong, Lance T. Pflieger, Sharan Paul, Mandi Gandelman, Karla P. Figueroa, Frank Rigo, C. Frank Bennett, Stefan M. Pulst
HUMAN MOLECULAR GENETICS
(2020)
Correction
Clinical Neurology
Laura Martinez-Palma, Ernesto Miquel, Valentina Lagos-Rodriguez, Luis Barbeito, Adriana Cassina, Patricia Cassina
Article
Anesthesiology
Valentina Lagos-Rodriguez, Laura Martinez-Palma, Soledad Marton, Ernesto Miquel, Ricardo Escobar-Pintos, Adriana Cassina, Natalia Lago, Patricia Cassina
Article
Cell Biology
Marcos Couto, Catalina Alamon, Maria Fernanda Garcia, Mariangeles Kovacs, Emiliano Trias, Susana Nievas, Emiliano Pozzi, Paula Curotto, Silvia Thorp, Maria Alejandra Dagrosa, Francesc Teixidor, Clara Vinas, Hugo Cerecetto
Article
Oncology
Catalina Alamon, Belen Davila, Maria Fernanda Garcia, Carina Sanchez, Mariangeles Kovacs, Emiliano Trias, Luis Barbeito, Martin Gabay, Nidal Zeineh, Moshe Gavish, Francesc Teixidor, Clara Vinas, Marcos Couto, Hugo Cerecetto
Article
Clinical Neurology
Sharan Paul, Warunee Dansithong, Karla P. Figueroa, Mandi Gandelman, Daniel R. Scoles, Stefan M. Pulst
Summary: The overabundance of STAU1 protein in multiple neurodegenerative diseases is associated with hyperactive mTOR; targeting STAU1 using RNAi can normalize mTOR levels, potentially providing a therapeutic avenue for diseases characterized by STAU1 overabundance.
ANNALS OF NEUROLOGY
(2021)
Article
Neurosciences
Jan Cendelin, Marija Cvetanovic, Mandi Gandelman, Hirokazu Hirai, Harry T. Orr, Stefan M. Pulst, Michael Strupp, Filip Tichanek, Jan Tuma, Mario Manto
Summary: SCAs are a group of hereditary degenerative diseases of the nervous system that often result in severe impairments of patients, without proven effective pharmacotherapies. Animal models, especially mice, have been essential in studying SCA pathogenesis and potential therapies, but each model has its strengths and weaknesses that require thorough phenotypic assessment and comparative studies for better translation to clinical trials. Mouse models complement cellular and invertebrate models in the research of complex neurological disorders like SCAs.
Article
Biochemistry & Molecular Biology
Mandi Gandelman, Warunee Dansithong, Stephen C. Kales, Sharan Paul, Gentrie Maag, Erika Aoyama, Alexey Zakharov, Ganesha Rai, Thomas Dexheimer, Brooke M. Whitehill, Hongmao Sun, Ajit Jadhav, Anton Simeonov, Mark J. Henderson, Duong P. Huynh, Stefan M. Pulst, Daniel R. Scoles
Summary: A-443654 was identified as a potent inhibitor of SNCA by screening compounds, and it effectively normalized levels of alpha-synuclein in cells with SNCA triplication and ATXN2-Q58. The inhibition of AKT by A-443654 also showed potential in reducing SNCA expression and treating Parkinson's disease pathology, by restoring cellular function and preventing alpha-synuclein toxicity.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Beatriz Sanchez-Calvo, Adriana Cassina, Mauricio Mastrogiovanni, Mariela Santos, Emiliano Trias, Eric E. Kelley, Homero Rubbo, Andres Trostchansky
Summary: The consumption of extra virgin olive oil has been shown to reduce the development of non-alcoholic fatty liver disease (NAFLD), with nitro-fatty acids potentially playing a key role in this benefit. Supplementation with olive oil and nitrite can improve liver mitochondrial function in mice and reduce fat liver accumulation.
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
(2021)
Review
Endocrinology & Metabolism
Patricia Cassina, Ernesto Miquel, Laura Martinez-Palma, Adriana Cassina
Summary: ALS is a human neurodegenerative disorder that leads to progressive muscle paralysis with no current cure. Recent studies suggest that changes in glial cell mitochondrial function are closely linked to disease progression in ALS, offering potential new therapeutic strategies.
NEUROIMMUNOMODULATION
(2021)
Article
Biochemistry & Molecular Biology
Daniel R. Scoles, Mandi Gandelman, Sharan Paul, Thomas Dexheimer, Warunee Dansithong, Karla P. Figueroa, Lance T. Pflieger, Scott Redlin, Stephen C. Kales, Hongmao Sun, David Maloney, Robert Damoiseaux, Mark J. Henderson, Anton Simeonov, Ajit Jadhav, Stefan M. Pulst
Summary: CAG repeat expansions in the ATXN2 gene are associated with SCA2 and ALS. Lowering ATXN2 transcription can potentially treat these diseases.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Clinical Neurology
Sharan Paul, Warunee Dansithong, Mandi Gandelman, Karla P. Figueroa, Tao Zu, Laura P. W. Ranum, Daniel R. Scoles, Stefan M. Pulst
Summary: This study reveals that the overabundance of stress granule (SG) protein STAU1 is associated with mTOR hyperactivation and impaired autophagy in various neurodegenerative diseases. Through its interaction with mTOR, STAU1 can increase mTOR levels, activate downstream targets, and impair autophagic flux. Thus, STAU1 may serve as a novel target for modulating mTOR activity and autophagy and for the treatment of neurodegenerative diseases.
ANNALS OF NEUROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Karla P. Figueroa, Collin J. Anderson, Sharan Paul, Warunee Dansithong, Mandi Gandelman, Daniel R. Scoles, Stefan M. Pulst
Summary: The shaker rat carries a naturally occurring mutation leading to progressive ataxia characterized by PC loss. In this study, the mutated gene underlying the shaker phenotype was identified as Slc9a6 through fine mapping and transcriptome analysis. It was confirmed that the shaker motor, molecular and cellular phenotypes could be reduced by AAV-based gene therapy targeting Slc9a6 expression. This suggests the potential of AAV-based gene therapy as a viable treatment strategy for Christianson syndrome caused by Slc9a6 mutation.
HUMAN MOLECULAR GENETICS
(2023)