Article
Biochemistry & Molecular Biology
Orietta Pansarasa, Maria Garofalo, Eveljn Scarian, Francesca Dragoni, Jessica Garau, Rosalinda Di Gerlando, Luca Diamanti, Matteo Bordoni, Stella Gagliardi
Summary: This review provides an overview of peripheral blood mononuclear cells (PBMCs) as a potential source of biomarkers in amyotrophic lateral sclerosis (ALS). It focuses on altered RNA metabolism and protein abnormalities, as well as the correlation between biological parameters and disease phenotypes. Although further studies are needed, PBMCs show great potential in ALS research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Marta Lualdi, Federico Casale, Mario Giorgio Rizzone, Maurizio Zibetti, Chiara Monti, Ilaria Colugnat, Andrea Calvo, Giovanni De Marco, Cristina Moglia, Giuseppe Fuda, Cristoforo Comi, Adriano Chio, Leonardo Lopiano, Mauro Fasano, Tiziana Alberio
Summary: Recent evidence supports an association between ALS and PD. Using proteomics, researchers obtained protein profiles from PBMCs of PD, ALS, and ALS-PK patients. Two protein classifiers were able to distinguish PD and ALS patients, as well as identify ALS-PK patients among ALS subjects, indicating different pathological pathways. Additionally, low levels of fibrinogen in PBMCs were confirmed as a characteristic feature of PD.
ACS CHEMICAL NEUROSCIENCE
(2023)
Article
Cell Biology
Cheng Li, Yu Zhu, Wenzhi Chen, Menghua Li, Mi Yang, Ziyang Shen, Yiyi Zhou, Lulu Wang, Huan Wang, Shu Li, Jiacheng Ma, Mengni Gong, Renshi Xu
Summary: This study proposes that the circulating NAD+ metabolism-derived gene signature can serve as a promising biomarker for predicting clinical outcomes in ALS patients. The abnormal activation of the NAD+ metabolic pathway is closely associated with prognosis in ALS. Additionally, the study finds a correlation between NPRS and the infiltration levels of various immune cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Natalia V. Belosludtseva, Lyudmila A. Matveeva, Konstantin N. Belosludtsev
Summary: Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by motor neuron death, muscle loss, and energy metabolism impairment. Mitochondria, which play a crucial role in cellular homeostasis, are early targets in ALS. Understanding mitochondrial turnover and function changes is important for improving ALS therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
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
Pharmacology & Pharmacy
Yujun Zhou, Jingshu Tang, Jiaqi Lan, Yong Zhang, Hongyue Wang, Qiuyu Chen, Yuying Kang, Yang Sun, Xinhong Feng, Lei Wu, Hongtao Jin, Shizhong Chen, Ying Peng
Summary: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with unmet medical needs. Honokiol (HNK) has therapeutic effects in other neurologic disease models and also showed protection in ALS disease models. Mechanistic studies revealed that HNK alleviated oxidative stress and improved mitochondrial function in ALS cells.
ACTA PHARMACEUTICA SINICA B
(2023)
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
Biology
Can Cui, Caroline Ingre, Li Yin, Xia Li, John Andersson, Christina Seitz, Nicolas Ruffin, Yudi Pawitan, Fredrik Piehl, Fang Fang
Summary: This study investigates the prognostic role of immune cells in amyotrophic lateral sclerosis (ALS). It finds that neutrophils and monocytes are associated with functional status, while natural killer cells and certain T lymphocyte subpopulations are prognostic markers for survival in ALS patients.
Article
Clinical Neurology
Francesco Gentile, Alessio Maranzano, Federico Verde, Veronica Bettoni, Eleonora Colombo, Alberto Doretti, Marco Olivero, Francesco Scheveger, Claudia Colombrita, Ilaria Bulgarelli, Edoardo Gioele Spinelli, Erminio Torresani, Stefano Messina, Luca Maderna, Federica Agosta, Claudia Morelli, Massimo Filippi, Vincenzo Silani, Nicola Ticozzi
Summary: This study investigates whether routine blood parameters can provide useful biomarkers for amyotrophic lateral sclerosis (ALS). The results show that creatinine is a reliable biomarker, associated with clinical features, disability, and survival in ALS patients. Markers of nutrition/inflammation may offer additional prognostic information, and AST and chloride could assist in predicting disease progression rate and survival.
JOURNAL OF NEUROLOGY
(2023)
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
Mengli Wang, Zhen Liu, Juan Du, Yanchun Yuan, Bin Jiao, Xuewei Zhang, Xuan Hou, Lu Shen, Jifeng Guo, Hong Jiang, Kun Xia, Jianguang Tang, Ruxu Zhang, Beisha Tang, Junling Wang
Summary: The study found no significant differences in serum immunoglobulin and complement levels between ALS patients and those with other neurodegenerative diseases, suggesting unique immune dysfunction in ALS. ALS patients had higher C4 levels, and IgG levels may be associated with disease onset age.
FRONTIERS IN NEUROLOGY
(2021)
Article
Oncology
Annette Bellar, Nicole Welch, Jaividhya Dasarathy, Amy Attaway, Ryan Musich, Avinash Kumar, Jinendiran Sekar, Saurabh Mishra, Yana Sandlers, David Streem, Laura E. Nagy, Srinivasan Dasarathy
Summary: Patients with acute alcohol-associated hepatitis (AH) have impaired immune function and abnormal mitochondrial function, leading to cellular senescence. Understanding these cellular changes is crucial for the understanding of the pathogenesis of AH.
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Giovanni Fajardo, Michael Coronado, Melia Matthews, Daniel Bernstein
Summary: Alterations in mitochondrial function and morphology are critical adaptations to cardiovascular stress, working in concert in an attempt to restore organelle-level and cellular-level homeostasis. Processes that alter mitochondrial morphology include fission, fusion, mitophagy, and biogenesis, and these interact to maintain mitochondrial quality control. Both pathological stressors like ischemia and physiological stressors like aerobic exercise can induce morphologic adaptations in mitochondria, but with different outcomes for mitochondrial health. Understanding the mechanisms underlying alterations in mitochondrial quality control under diverse cardiovascular stressors can aid in developing pharmacologic interventions for restoring cellular homeostasis.
Review
Clinical Neurology
Stanley H. Appel, David R. Beers, Weihua Zhao
Summary: In ALS, motor neuron cell death is initiated by multiple cell autonomous pathways leading to noncell autonomous inflammatory reactivity. This results in activated microglia, astrocytes, and pro-inflammatory innate and adaptive immune cells in patients. Dysregulation of cells and cytokines accurately reflect disease burdens, progression rates, and survival times in ALS, indicating potential therapeutic targets in systemic pro-inflammatory responses.
CURRENT OPINION IN NEUROLOGY
(2021)
Article
Biology
Maria Inmaculada Dominguez-Mozo, Maria Celeste Garcia-Frontini Nieto, Maria Isabel Gomez-Calcerrada, Silvia Perez-Perez, Maria Angel Garcia-Martinez, Luisa Maria Villar, Noelia Villarrubia, Lucienne Costa-Frossard, Rafael Arroyo, Roberto Alvarez-Lafuente
Summary: This study compared the mitochondrial function of peripheral blood cells in MS patients and healthy donors, and found signs of mitochondrial impairment in MS patients, especially in those with lipid-specific oligoclonal immunoglobulin M bands. These findings contribute to a better understanding of the physiopathology of MS.
Article
Biochemistry & Molecular Biology
Luana Naia, Catarina Carmo, Susanna Campesan, Ligia Fao, Victoria E. Cotton, Jorge Valero, Carla Lopes, Tatiana R. Rosenstock, Flaviano Giorgini, A. Cristina Rego
Summary: The study demonstrates that SIRT3 plays a neuroprotective role in Huntington's disease by regulating oxidative stress and mitochondrial function, suggesting a potential therapeutic target for the disease.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Neurosciences
Amanda Siena, Jessica Mayumi Camargo Yuzawa, Aline Camargo Ramos, Elisandra Henrique, Mariana Dutra Brito, Mariana Bendlin Calvazara, Tatiana Rosado Rosenstock
Summary: Study showed that inhibiting mitochondria during critical neurodevelopment in rodents can lead to psychiatric-like behaviors and alterations in synaptic proteins in adulthood. These changes may be due to adjustments in the CREB pathway and alterations in mitochondrial biogenesis and Nrf1 expression.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Plant Sciences
Victoria Caroline Bottino Pontes, Juliana Pereira Tavares de Melo Tavares, Tatiana Rosado Rosenstock, Domingos Savio Rodrigues, Marcelo Icimoto Yudi, Jaqueline Pereira Moura Soares, Suzana Costa Ribeiro, Rafael Sutti, Luce Maria Brandao Torres, Fabiana Henriques Machado de Melo, Maria Thereza Gamberini
Summary: The study found that AE has a positive impact on blood flow in rats in vivo, but does not directly affect the vasodilation response induced by endothelial cells in vitro. Additionally, the highest concentrations of AE were found to negatively affect nitric oxide levels, potentially due to Akt phosphorylation inhibition.
JOURNAL OF ETHNOPHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Amy Kim, Kathryn Lalonde, Aaron Truesdell, Priscilla Gomes Welter, Patricia S. Brocardo, Tatiana R. Rosenstock, Joana Gil-Mohapel
Summary: Huntington's disease is a neurodegenerative disorder caused by a CAG expansion in the HD gene, with symptoms typically appearing in mid-life involving cognitive deficits and motor disturbances. Despite known genetic cause, multiple mechanisms are believed to contribute to neurodegeneration, leading to various pre-clinical and clinical studies testing therapeutic approaches.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Thiago Garcia Varga, Juan Guilherme de Toledo Simoes, Amanda Siena, Elisandra Henrique, Regina Claudia Barbosa da Silva, Vinicius dos Santos Bioni, Aline Camargo Ramos, Tatiana Rosado Rosenstock
Summary: The study demonstrates that newborn rats treated with rotenone exhibit behaviors similar to psychosis in adulthood and show responsiveness to haloperidol but not methylphenidate.
PSYCHOPHARMACOLOGY
(2021)
Article
Medicine, General & Internal
Teresa Cunha-Oliveira, Daniela Franco Silva, Luis Segura, Ines Baldeiras, Ricardo Marques, Tatiana Rosenstock, Paulo J. Oliveira, Filomena S. G. Silva
Summary: Distinct redox signatures were found in lymphoblasts from mutSOD1, undSOD1, and healthy controls, which can serve as therapeutic targets for ALS drug development. High heterogeneity in redox profiles between cohorts was observed, but clustering analysis successfully segregated healthy controls from ALS samples based on specific parameters. These findings provide valuable insights for understanding oxidative stress profiles in different forms of ALS and potential treatment strategies.
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Behavioral Sciences
Rodolpho Pereira de Oliveira, Thais Yokoyama, Lucas de Santana Cardoso Thomaz, Jose Simoes de Andrade, Alexia dos Anjos Santos, Vinicius de Carvalho Mendonca, Tatiana Rosenstock, Marinete Pinheiro Carrera, Priscila Medeiros, Fabio Cardoso Cruz, Norberto Cysne Coimbra, Regina Claudia Barbosa Silva
Summary: The relationship between serotonin dysfunction and schizophrenia began with the discovery of the effects of LSD on 5-HT2A receptors. Activation of these receptors leads to perceptual and behavioral changes. This study investigated the neural pathway between IC and PPTg, as well as the effects of DOI and bicuculline on PPI responses. The results suggest that IC 5-HT2A receptors may play a role in the regulation of inhibitory pathways mediating PPI response in IC and PPTg structures.
BEHAVIOURAL BRAIN RESEARCH
(2023)
Article
Neurosciences
Luiz Felipe Souza e Silva, Amanda Siena, Jessica Mayumi Yuzawa, Jorge Luiz de Barros Torresi, Alan Ziroldo, Tatiana Rosado Rosenstock
Summary: This study evaluated whether modulators of sirtuins could serve as a neuroprotective strategy for alleviating mitochondrial deregulation induced by hypoxia. The findings suggest that sirtuin modulation can reduce cell death, improve mitochondrial structure and function, and have important implications for neurodevelopmental disorders caused by environmental factors.
Article
Cell Biology
Congxin Sun, Elena Seranova, Malkiel A. Cohen, Miruna Chipara, Jennie Roberts, Dewi Astuti, Adina M. Palhegyi, Animesh Acharjee, Lucia Sedlackova, Tetsushi Kataura, Elsje G. Otten, Prashanta K. Panda, Samuel Lara-Reyna, Miriam E. Korsgen, Kevin J. Kauffman, Alejandro Huerta-Uribe, Malgorzata Zatyka, Luiz F. S. E. Silva, Jorge Torresi, Shupei Zhang, Georgina W. Hughes, Carl Ward, Erich R. Kuechler, David Cartwright, Sergey Trushin, Eugenia Trushina, Gaurav Sahay, Yosef Buganim, Gareth G. Lavery, Joerg Gsponer, Daniel G. Anderson, Eva-Maria Frickel, Tatiana R. Rosenstock, Timothy Barrett, Oliver D. K. Maddocks, Daniel A. Tennant, Haoyi Wang, Rudolf Jaenisch, Viktor I. Korolchuk, Sovan Sarkar
Summary: Autophagy is a crucial process for cellular survival, and its dysfunction is associated with human diseases like neurodegeneration. In this study, autophagy-deficient neurons were generated to investigate the impact of autophagy loss on neuronal survival. It was found that autophagy-deficient neurons exhibited basal cytotoxicity and metabolic defects. Depletion of NAD due to hyperactivation of NAD-consuming enzymes triggered cell death in these neurons. Boosting intracellular NAD levels improved cell viability by restoring mitochondrial bioenergetics and proteostasis. These findings provide mechanistic insights into the link between autophagy deficiency and neuronal cell death, offering potential therapeutic targets for neurodegenerative and lysosomal storage diseases with autophagic defects.
Article
Cell & Tissue Engineering
Malgorzata Zatyka, Tatiana R. Rosenstock, Congxin Sun, Adina M. Palhegyi, Georgina W. Hughes, Samuel Lara-Reyna, Dewi Astuti, Alessandro di Maio, Axel Sciauvaud, Miriam E. Korsgen, Vesna Stanulovic, Gamze Kocak, Malgorzata Rak, Sandra Pourtoy-Brasselet, Katherine Winter, Thiago Varga, Margot Jarrige, Helene Polveche, Joao Correia, Eva-Maria Frickel, Maarten Hoogenkamp, Douglas G. Ward, Laetitia Aubry, Timothy Barrett, Sovan Sarkar
Summary: Wolfram syndrome (WS) is a rare early-onset neurodegenerative disease that is associated with mitochondrial abnormalities. The loss of interaction between WFS1 and VDAC1 in WS cells can compromise mitochondrial function, but restoring WFS1 levels can improve mitochondrial function and network. Therefore, targeting WFS1 or modulating mitochondrial function may provide a therapeutic intervention for WS and similar diseases.