Article
Cell Biology
Hualing Peng, Jingyi Zhang, Amanda Ya, Winston Ma, Sammy Villa, Shahar Sukenik, Xuecai Ge
Summary: This study identified a new regulatory mechanism of the Hh pathway involving the interaction between PDE4D3 and Mmg, and how Mmg loss can suppress the growth of MB, providing a promising therapeutic avenue for Hh-related cancers with reduced side effects.
MOLECULAR BIOLOGY OF THE CELL
(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
Clinical Neurology
Imogen J. Swift, Simon Sjodin, Johan Gobom, Ann Brinkmalm, Kaj Blennow, Henrik Zetterberg, Jonathan D. Rohrer, Aitana Sogorb-Esteve
Summary: Increasing evidence suggests a link between endo-lysosomal dysfunction and frontotemporal dementia (FTD). A study quantified 18 proteins in the cerebrospinal fluid of patients with different variants of primary progressive aphasia (PPA) and found differential alterations in lysosomal proteins among the PPA variants.
JOURNAL OF NEUROLOGY
(2023)
Article
Cell Biology
Abubakar Wani, Jiang Zhu, Jason D. Ulrich, Abdallah Eteleeb, Andrew D. Sauerbeck, Sydney J. Reitz, Khalid Arhzaouy, Chiseko Ikenaga, Carla M. Yuede, Sara K. Pittman, Feng Wang, Shan Li, Bruno A. Benitez, Carlos Cruchaga, Terrance T. Kummer, Oscar Harari, Tsui-Fen Chou, Rolf Schroder, Christoph S. Clemen, Conrad C. Weihl
Summary: Inactivating VCP and expressing disease-associated mutations in a mouse model revealed that loss of VCP-dependent functions is a mediator of FTLD-TDP, with unexpected biochemical similarity to progranulin deficiency.
Article
Biochemistry & Molecular Biology
Viviana Villa, Giulia Montalto, Francesca Caudano, Ernesto Fedele, Roberta Ricciarelli
Summary: Tau protein can form hyperphosphorylated aggregates in neurodegenerative diseases like Alzheimer's, and phosphorylation of tau by cAMP-dependent protein kinase A (PKA) at Ser214 reduces its pathological assembly. The activation of adenylyl cyclase increases pTAU-S214 levels in N2a cells and rat hippocampal slices, and this effect is mimicked by GEBR-7b, a phosphodiesterase 4D inhibitor.
Article
Biochemistry & Molecular Biology
Todd Logan, Matthew J. Simon, Anil Rana, Gerald M. Cherf, Ankita Srivastava, Sonnet S. Davis, Ray Lieh Yoon Low, Chi-Lu Chiu, Meng Fang, Fen Huang, Akhil Bhalla, Ceyda Llapashtica, Rachel Prorok, Michelle E. Pizzo, Meredith E. K. Calvert, Elizabeth W. Sun, Jennifer Hsiao-Nakamoto, Yashas Rajendra, Katrina W. Lexa, Devendra B. Srivastava, Bettina van Lengerich, Junhua Wang, Yaneth Robles-Colmenares, Do Jin Kim, Joseph Duque, Melina Lenser, Timothy K. Earr, Hoang Nguyen, Roni Chau, Buyankhishig Tsogtbaatar, Ritesh Ravi, Lukas L. Skuja, Hilda Solanoy, Howard J. Rosen, Bradley F. Boeve, Adam L. Boxer, Hilary W. Heuer, Mark S. Dennis, Mihalis S. Kariolis, Kathryn M. Monroe, Laralynne Przybyla, Pascal E. Sanchez, Rene Meisner, Dolores Diaz, Kirk R. Henne, Ryan J. Watts, Anastasia G. Henry, Kannan Gunasekaran, Giuseppe Astarita, Jung H. Suh, Joseph W. Lewcock, Sarah L. DeVos, Gilbert Di Paolo
Summary: Mutations in the GRN gene lead to frontotemporal dementia, with a deficiency in the PGRN protein being the cause. Research found various abnormalities in Grn(-/-) mice, including a lack of endolysosomal phospholipids and accumulation of glucocerebrosidase substrate. A protein replacement strategy corrected these abnormalities and may represent a potential biotherapeutic for GRN-FTD.
Article
Neurosciences
Vanesa Pytel, Maria Nieves Cabrera-Martin, Alfonso Delgado-Alvarez, Jose Luis Ayala, Paloma Balugo, Cristina Delgado-Alonso, Miguel Yus, Maria Teresa Carreras, Jose Luis Carreras, Jorge Matias-Guiu, Jordi A. Matias-Guiu
Summary: This study found that using personalized targeting repetitive transcranial magnetic stimulation can improve language ability, patient and caregiver perception of change, apathy, and depression in patients with PPA, and there is an increase in metabolism in various brain regions after treatment, indicating enhancement of synaptic activity.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Multidisciplinary Sciences
Itika Saha, Patricia Yuste-Checa, Miguel Da Silva Padilha, Qiang Guo, Roman Koerner, Hauke Holthusen, Victoria A. Trinkaus, Irina Dudanova, Ruben Fernandez-Busnadiego, Wolfgang Baumeister, David W. Sanders, Saurabh Gautam, Marc I. Diamond, F. Ulrich Hartl, Mark S. Hipp
Summary: This study identifies VCP as a core component in the machinery for removing neurodegenerative disease aggregates, and suggests that its activity may be associated with enhanced aggregate spreading in tauopathies.
NATURE COMMUNICATIONS
(2023)
Review
Cell Biology
Xinwa Jiang, Ariana Gatt, Tammaryn Lashley
Summary: Frontotemporal dementia (FTD) is the second most common form of early-onset dementia, characterized by behavioral, executive, and/or language impairment. Frontotemporal lobar degeneration (FTLD) is the main cause of FTD and is associated with the abnormal accumulation of proteins like tau, TAR DNA-binding protein 43 (TDP-43), and fused in sarcoma (FUS). Recent studies have expanded the exploration of the relationship between other heterogeneous ribonucleic acid proteins (hnRNPs) and FTLD pathology, revealing the association between hnRNP abnormalities and FTLD. These findings highlight the important role of multiple hnRNPs in the development of FTLD and suggest the need for further research on this protein family.
Article
Clinical Neurology
Yuri Matteo Falzone, Teuta Domi, Alessandra Mandelli, Laura Pozzi, Paride Schito, Tommaso Russo, Alessandra Barbieri, Raffaella Fazio, Maria Antonietta Volonte, Giuseppe Magnani, Ubaldo Del Carro, Paola Carrera, Andrea Malaspina, Federica Agosta, Angelo Quattrini, Roberto Furlan, Massimo Filippi, Nilo Riva
Summary: NfL is a useful biomarker for the diagnosis of ALS and the strongest predictor of survival. UCHL1 is an independent prognostic factor helpful in stratifying survival in patients with low NfL levels, likely to have slowly progressive disease. GFAP reflects extramotor involvement, namely cognitive impairment or frontotemporal dementia.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Neurosciences
Yuxing Xia, Brach M. M. Bell, Justin D. D. Kim, Benoit I. I. Giasson
Summary: Tauopathies are neurodegenerative diseases characterized by the formation of tau brain aggregates. Imbalance of 3R and 4R tau isoforms is a contributing factor in the development of these diseases. The S356T tau mutation shows unique prion-like seeded aggregation, forming extensive Thioflavin positive aggregates. This finding will contribute to the understanding of diverse presentations of different tauopathies.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Evelien Van Schoor, Mathieu Vandenbulcke, Valerie Bercier, Rik Vandenberghe, Julie van der Zee, Christine Van Broeckhoven, Markus Otto, Bernard Hanseeuw, Philip Van Damme, Ludo Van den Bosch, Dietmar Rudolf Thal
Summary: This study reports a novel frameshift mutation in the TUBA4A gene in a patient with semantic variant of primary progressive aphasia, suggesting a potential loss-of-function pathogenic mechanism associated with frontotemporal lobar degeneration (FTLD). The findings support the idea that N-terminal TUBA4A mutations are linked to FTLD-TDP.
Article
Cell Biology
Karima Schwab, Valeria Melis, Charles R. Harrington, Claude M. Wischik, Mandy Magbagbeolu, Franz Theuring, Gernot Riedel
Summary: The research found that treatment with hydromethylthionine could reverse some behavioral deficiencies and abnormal aggregation of tau protein in tau-transgenic mice. Results suggest that hydromethylthionine can restore cellular activity through pathways such as metabolic/mitochondrial dysfunction, synaptic transmission, and stress responses, leading to an improvement in overall function of the FTD brain.
Article
Multidisciplinary Sciences
Carolina Alquezar, Kathleen M. Schoch, Ethan G. Geier, Eliana Marisa Ramos, Aurora Scrivo, Kathy H. Li, Andrea R. Argouarch, Elisabeth E. Mlynarski, Beth Dombroski, Michael DeTure, Dennis W. Dickson, Jennifer S. Yokoyama, Ana M. Cuervo, Alma L. Burlingame, Gerard D. Schellenberg, Timothy M. Miller, Bruce L. Miller, Aimee W. Kao
Summary: Genetic variants in TSC1 decrease TSC1/hamartin levels, leading to tau accumulation and susceptibility to tauopathies, by modulating p300 and SIRT1 enzymes, tau levels can be restored.
Article
Neurosciences
Nuole Zhu, Miguel Santos-Santos, Ignacio Illan-Gala, Victor Montal, Teresa Estelles, Isabel Barroeta, Miren Altuna, Javier Arranz, Laia Munoz, Olivia Belbin, Isabel Sala, Maria Belen Sanchez-Saudinos, Andrea Subirana, Laura Videla, Jordi Pegueroles, Rafael Blesa, Jordi Clarimon, Maria Carmona-Iragui, Juan Fortea, Alberto Lleo, Daniel Alcolea
Summary: This study found that plasma GFAP and plasma neurofilament light chain levels differ in frontotemporal dementia and Alzheimer's disease, and their combination is useful for distinguishing between the two diseases. In FTD patients, plasma GFAP is correlated with cognition, CSF and plasma NfL, and cortical thickness. Higher tertile of plasma GFAP is associated with greater cognitive decline during follow-up in FTD and AD patients.
TRANSLATIONAL NEURODEGENERATION
(2021)
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)
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
Neurosciences
Virginie Bottero, Jose A. Santiago, James P. Quinn, Judith A. Potashkin
Summary: This study directly investigates the root cause of ALS by examining the changes in gene expression in degenerated motor neurons of ALS patients. It identifies 610 switch genes enriched in several pathways and identifies ELK1 and GATA2 as key regulators. Potential therapeutics for ALS are also suggested. Furthermore, the study highlights metals and organic compounds as possible mediators of neurodegeneration.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(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)
