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)
Review
Biochemistry & Molecular Biology
Bradley Roberts, Frances Theunissen, Francis L. Mastaglia, P. Anthony Akkari, Loren L. Flynn
Summary: This review provides a comprehensive overview of the literature on the etiology and development of ALS, as well as its commonalities with synucleinopathy disorders. It discusses the involvement of alpha Syn in ALS and motor neuron disease pathology, along with current theories and strategies for therapeutics in ALS treatment, with a focus on small molecule RNA technologies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biology
Sang Hwa Kim, Kye D. Nichols, Eric N. Anderson, Yining Liu, Nandini Ramesh, Weiyan Jia, Connor J. Kuerbis, Mark Scalf, Lloyd M. Smith, Udai Bhan Pandey, Randal S. Tibbetts, Jeannie Chin
Summary: Mutations in UBQLN2 cause X-linked forms of ALS and FTD, but the underlying mechanisms are unknown. Studying ALS-associated mutants of UBQLN2 in Drosophila, it was found that they trigger heat stress-dependent neurodegeneration. A genetic modifier screen identified endolysosomal and axon guidance genes, including the netrin receptor Unc-5, as key regulators of UBQLN2 toxicity. Reduced dosage of Unc-5 or its coreceptor Dcc/frazzled alleviated neurodegenerative phenotypes in flies expressing UBQLN2(ALS) alleles. Further experiments using iPSCs and iMNs demonstrated lysosomal defects and cytosolic UBQLN2 inclusions, neurite complexity reduction, and growth cone defects, which were partially reversed by silencing of UNC5B and DCC. These findings suggest altered growth cone dynamics as a conserved pathomechanism in UBQLN2-associated ALS/FTD.
Review
Pharmacology & Pharmacy
Yvonne E. Klingl, Donya Pakravan, Ludo Van den Bosch
Summary: ALS is a devastating neurodegenerative disease with limited treatment options. Research suggests that interference with histone deacetylases may be helpful in treating ALS.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Review
Neurosciences
Koy Chong Ng Kee Kwong, Pratap K. Harbham, Bhuvaneish T. Selvaraj, Jenna M. Gregory, Suvankar Pal, Giles E. Hardingham, Siddharthan Chandran, Arpan R. Mehta
Summary: This review summarizes the 40-year history of CSF toxicity studies in ALS and discusses various proposed mechanisms such as glutamate excitotoxicity, proteotoxicity, and oxidative stress. The potential implications of a toxic CSF circulatory system in the pathophysiology of ALS and its significance in current ALS research are also considered.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Review
Biochemistry & Molecular Biology
Soju Seki, Yoshihiro Kitaoka, Sou Kawata, Akira Nishiura, Toshihiro Uchihashi, Shin-ichiro Hiraoka, Yusuke Yokota, Emiko Tanaka Isomura, Mikihiko Kogo, Susumu Tanaka
Summary: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the degeneration of motor neurons, with emerging evidence suggesting involvement of sensory neurons. Clinical research has shown sensory symptoms and abnormal nerve conduction in ALS patients, while preclinical research has identified genetic abnormalities in both sensory and motor neurons. This review highlights the potential of targeting sensory neuron abnormalities in ALS for new therapies.
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
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)
Article
Medicine, General & Internal
Wen-Chao Liu, Na Liu, Yan Wang, Chen Huang, Yan-Fang Li, Hao Wang, Xiao-Gang Li, Min Deng
Summary: Research shows that motor neurons (MNs) derived from ALS patient-specific iPSC lines can replicate key aspects of ALS pathogenesis, providing insights into the disease's pathophysiological processes. Incremental mutant expressions of SOD1 in MNs may disrupt cellular function, leading to intracellular calcium disturbances and contributing to the onset of the disease.
CHINESE MEDICAL JOURNAL
(2021)
Article
Neurosciences
Thorsten Lichtenstein, Alina Sprenger, Kilian Weiss, Nils Grosse Hokamp, David Maintz, Marc Schlamann, Gereon R. Fink, Helmar C. Lehmann, Tobias D. Henning
Summary: The study demonstrated that ALS patients had significantly lower fractional anisotropy values in the sciatic nerve and higher intramuscular fat fractions in the quadriceps femoris muscle compared to healthy controls, indicating potential structural nerve damage and muscle changes in ALS that can be assessed using multiparametric MRI protocols.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Oluwamolakun Bankole, Ilaria Scambi, Edoardo Parrella, Matilde Muccilli, Roberta Bonafede, Ermanna Turano, Marina Pizzi, Raffaella Mariotti
Summary: This study demonstrates the beneficial effects of combined treatment with valproate and resveratrol in ALS mice, with a sexually dimorphic response. The combination of drugs restores NF-kB to its neuroprotective state, reducing pathology and symptoms, and prolonging survival.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, General & Internal
Christine Zizzi, Jamison Seabury, Spencer Rosero, Danae Alexandrou, Ellen Wagner, Jennifer S. Weinstein, Anika Varma, Nuran Dilek, John Heatwole, Joanne Wuu, James Caress, Richard Bedlack, Volkan Granit, Jeffrey M. Statland, Paul Mehta, Michael Benatar, Chad Heatwole
Summary: This study used data from two multi-center randomized controlled trials and found that depression symptoms in patients can be categorized into four clusters, which have differential responses to repetitive transcranial magnetic stimulation (rTMS) treatment. Further research aims to personalize rTMS protocols based on individual clinical presentations.
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
Clinical Neurology
Melina Pazian Martins, Carelis Gonzalez-Salazar, Fabricio Diniz de Lima, Tauana Bernardes Leoni, Alberto R. M. Martinez, Joao Pedro Nunes Goncalves, Anamarli Nucci, Marcondes Cavalcante Franca Jr
Summary: This study characterized and compared the autonomic function of patients with sporadic ALS and familial ALS type 8. The results showed that both types of ALS patients had dysautonomia involving both sympathetic and parasympathetic divisions, but the symptoms were different between the two groups.
CLINICAL NEUROPHYSIOLOGY
(2023)
Article
Neurosciences
Cristian Arredondo, Carolina Cefaliello, Agnieszka Dyrda, Nur Jury, Pablo Martinez, Ivan Diaz, Armando Amaro, Helene Tran, Danna Morales, Maria Pertusa, Lorelei Stoica, Elsa Fritz, Daniela Corvalan, Sebastian Abarzua, Maxs Mendez-Ruette, Paola Fernandez, Fabiola Rojas, Meenakshi Sundaram Kumar, Rodrigo Aguilar, Sandra Almeida, Alexandra Weiss, Fernando J. Bustos, Fernando Gonzalez-Nilo, Carolina Otero, Maria Florencia Tevy, Daryl A. Bosco, Juan C. Saez, Thilo Kahne, Fen-Biao Gao, James D. Berry, Katharine Nicholson, Miguel Sena-Esteves, Rodolfo Madrid, Diego Varela, Martin Montecino, Robert H. Brown, Brigitte van Zundert
Summary: Non-cell-autonomous mechanisms, specifically the release of unidentified toxic factors by astrocytes, contribute to the neurodegenerative diseases ALS and FTD. Studies found that astrocytes with ALS/FTD-related mutations display elevated levels of intracellular inorganic polyphosphate (polyP), which is also present in astrocyte-conditioned media (ACM). Degradation or neutralization of polyP in ALS/FTD astrocytes or ACM prevents the death of motoneurons. Additionally, polyP staining signals are enriched in postmortem ALS spinal cord sections and ALS cerebrospinal fluid (CSF) exhibits increased concentrations of polyP, suggesting polyP as a potential therapeutic target and biomarker for ALS/FTD.
Article
Geriatrics & Gerontology
Jose A. Santiago, Virginie Bottero, Judith A. Potashkin
FRONTIERS IN AGING NEUROSCIENCE
(2018)
Article
Neurosciences
Virginie Bottero, Jose A. Santiago, Judith A. Potashkin
JOURNAL OF PARKINSONS DISEASE
(2018)
Article
Multidisciplinary Sciences
Judith A. Potashkin, Virginie Bottero, Jose A. Santiago, James P. Quinn
Article
Neurosciences
Jose A. Santiago, Virginie Bottero, Judith A. Potashkin
FRONTIERS IN NEUROSCIENCE
(2019)
Article
Biochemistry & Molecular Biology
Jose A. Santiago, Virginie Bottero, Judith A. Potashkin
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Biochemistry & Molecular Biology
Judith A. Potashkin, Virginie Bottero, Jose A. Santiago, James P. Quinn
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Review
Geriatrics & Gerontology
Jose A. Santiago, Judith A. Potashkin
Summary: Alzheimer's disease (AD) is often accompanied by a variety of other chronic diseases, including diabetes and cardiovascular disease, which may increase the risk of AD. Research suggests that disruption in several shared biological pathways could be the underlying mechanism for the association between AD and these comorbidities. Inflammation is considered a common dysregulated pathway shared by most comorbidities associated with AD.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Jose A. Santiago, James P. Quinn, Judith A. Potashkin
Summary: This study identified switch genes associated with drastic transcriptomic changes in ALS patients' blood, revealing potential sex-specific roles in the disease mechanism, with males showing metabolic pathway enrichment and females related to infectious diseases and inflammation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Virginie Bottero, Fahed Alrafati, Jose A. Santiago, Judith A. Potashkin
Summary: Frontotemporal lobar degeneration (FTLD) or frontotemporal dementia (FTD) is characterized by a progressive decline in executive function, affecting approximately 50-60,000 Americans. There are familial and sporadic forms of FTD, with GRN progranulin and C9orf72 mutations being common causes. Dysregulated genes in FTD are mainly found in the frontal cortex and Brodmann's area 8, with different signaling pathways associated with familial and sporadic forms. Therapeutic agents such as valproic acid may be beneficial in treating patients with FTD.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Jose A. Santiago, James P. Quinn, Judith A. Potashkin
Summary: Physical activity has been found to have beneficial effects on brain health by offsetting cognitive decline and dementia. This study used bioinformatic methods to analyze the molecular mechanisms of physical activity in the brain. The results show that physical activity influences transcriptional changes in the brain through different pathways, providing neuroprotection in various neurodegenerative diseases by modulating protein processing, metabolic control, and synaptic signaling pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Geriatrics & Gerontology
Jose A. Santiago, James P. Quinn, Judith A. Potashkin
Summary: Sex-specific differences may contribute to the development of Alzheimer's disease, but the molecular mechanisms behind these differences are not well characterized. This study analyzed transcriptional changes in the brain of AD patients and identified sex-specific signatures and pathways that may be involved in AD progression.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Jose A. Santiago, James P. Quinn, Judith A. Potashkin
Summary: Loneliness and social isolation have negative effects on mental health, and can lead to cognitive impairment and neurodegenerative diseases. Through bioinformatics analysis, we identified molecular mechanisms and genes associated with loneliness, which are also linked to neuropsychiatric and neurodegenerative diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Geriatrics & Gerontology
Jose A. Santiago, Judith A. Potashkin
Summary: Neurodegenerative diseases have increased significantly in the past decade. Physical activity has emerged as the most accessible lifestyle modification to combat cognitive decline and neurodegeneration. This review discusses the potential of lifestyle modifications, including physical activity, diet, cognitive training, and sleep hygiene, to treat and prevent neurodegenerative diseases based on epidemiological, clinical, and molecular studies.
FRONTIERS IN AGING NEUROSCIENCE
(2023)
Review
Biochemistry & Molecular Biology
Jose A. Santiago, Mridula Karthikeyan, Madison Lackey, Diana Villavicencio, Judith A. Potashkin
Summary: Diabetes is associated with an increased risk and progression of Alzheimer's and Parkinson's diseases, but may confer neuroprotection against amyotrophic lateral sclerosis. Perturbations in glucose and insulin regulation, cholesterol metabolism, and mitochondrial bioenergetics defects could underlie the molecular mechanisms of diabetes on the brain.
TRENDS IN MOLECULAR MEDICINE
(2023)