Review
Biochemistry & Molecular Biology
Alberto Piperno, Sara Pelucchi, Raffaella Mariani
Summary: Ferritin is a widely-present cytosolic protein that binds and stores iron in cells. Its measurement in serum can be used to evaluate iron storage, but interpretation is complicated by various factors. Hyperferritinemia, an elevated serum ferritin level, can be caused by a range of genetic and acquired conditions associated with iron metabolism. Diagnosis involves medical history, genetic tests, and evaluating liver iron levels. This review focuses on inherited hyperferritinemia with or without iron overload and provides a step-by-step approach to distinguish it from acquired forms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Matthew K. Boag, Angus Roberts, Vladimir N. Uversky, Linlin Ma, Des R. Richardson, Dean L. Pountney
Summary: A major hallmark of Parkinson's disease is the destruction of dopaminergic neurons in the substantia nigra pars compacta. This destruction is preceded by the formation of Lewy bodies, composed of alpha-synuclein aggregates. The accumulation of alpha-synuclein, iron, and mitochondrial dysfunction affects the nigral neurons. The mechanisms underlying iron accumulation are not well understood. This review explores the relationship between iron regulation and alpha-synuclein and discusses the potential therapeutic targets in the context of Parkinson's disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
L. Ma, M. Gholam Azad, M. Dharmasivam, V Richardson, R. J. Quinn, Y. Feng, D. L. Pountney, K. F. Tonissen, G. D. Mellick, I Yanatori, D. R. Richardson
Summary: Studies indicate dysregulation of iron metabolism in Parkinson's disease, leading to increased neuronal iron levels and iron-mediated reactive oxygen species. Therapies utilizing limited iron chelation have shown success in treating PD. Further advancements in treatment are possible once the molecular pathways of iron processing are fully understood.
Review
Medical Laboratory Technology
Erin S. Grant, Danielle B. Clucas, Gawain McColl, Liam T. Hall, David A. Simpson
Summary: Iron is crucial for human health, but both deficiency and overload can cause health concerns. The measurement of total iron stores is essential for identifying abnormal iron levels and tracking changes in clinical settings.
CLINICAL CHEMISTRY AND LABORATORY MEDICINE
(2021)
Review
Medicine, General & Internal
Paul C. Adams, Gary Jeffrey, John Ryan
Summary: Haemochromatosis is a common genetic disease in patients of northern European ancestry. It is often misdiagnosed in patients without iron overload and underdiagnosed in many patients. Early diagnosis through genetic testing and treatment with periodic phlebotomy can prevent serious complications such as liver cirrhosis, liver cancer, and death. This Seminar provides an update on the origins of haemochromatosis and covers pathophysiology, genetics, natural history, signs and symptoms, differential diagnoses, treatment with phlebotomy, outcomes, and future directions.
Article
Neurosciences
Lena H. P. Vroegindeweij, Piotr A. Wielopolski, Agnita J. W. Boon, J. H. Paul Wilson, Rob M. Verdijk, Sipeng Zheng, Sylvestre Bonnet, Lucia Bossoni, Louise van der Weerd, Juan A. Hernandez-Tamames, Janneke G. Langendonk
Summary: The study validated R 2 * as a quantitative measure of brain iron content in aceruloplasminemia, showing a linear association between R 2 * and iron concentration, and high sensitivity to variations in iron concentration in severely iron-loaded brains.
Article
Clinical Neurology
M. Kurzawa-Akanbi, M. Keogh, E. Tsefou, L. Ramsay, M. Johnson, S. Keers, L. W. S. A. Ochieng, A. McNair, P. Singh, A. Khan, A. Pyle, G. Hudson, P. G. Ince, J. Attems, J. Burn, P. F. Chinnery, C. M. Morris
Summary: Neuroferritinopathy (NF) or hereditary ferritinopathy (HF) is an autosomal dominant movement disorder caused by a mutation in the iron storage protein ferritin. Study of HF suggests that, in addition to iron accumulation, the disorder also presents characteristics of a protein aggregation disorder, with no evidence of age-related neurodegenerative pathology, oxidative stress activation, or significant mitochondrial pathology. This sheds light on other neurodegenerative diseases characterized by iron deposition.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Anja Reinert, Tilo Reinert, Thomas Arendt, Markus Morawski
Summary: A subpopulation of neurons, characterized by a special extracellular matrix composition forming a perineuronal net (PN) with a high affinity to iron, is less vulnerable to iron-induced oxidative stress and neurodegeneration. These PN+ neurons have higher intracellular iron concentrations and increased levels of iron proteins, with the iron concentration of the PN itself not being increased. The properties of these resilient pacemaker neurons with bustling iron metabolism and outstanding iron handling capabilities contribute to their low vulnerability to iron-induced oxidative stress and degeneration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Erin S. Grant, Liam T. Hall, Lloyd C. L. Hollenberg, Gawain McColl, David A. Simpson
Summary: In this study, the magnetic properties of ferritin, the primary storage protein in the body, were systematically studied using diamond-based quantum spin relaxometry. An anomalous magnetic behavior was observed at relatively low iron loads due to a morphological change in the iron core of ferritin. The inclusion of this morphological change in a theoretical model was supported by electron microscopy studies and provided evidence for the magnetic consequence of the morphological change.
Review
Biochemistry & Molecular Biology
Stephanie L. Baringer, Ian A. Simpson, James R. Connor
Summary: Brain iron homeostasis is crucial for neurological health, and its imbalance is associated with various neurological disorders. Proper regulation of iron entry into the brain via transferrin and H-ferritin is important due to the detrimental effects of unrestricted iron. This review discusses the mechanisms of iron transport regulation at the blood-brain barrier and explores the dysregulation of brain iron in Alzheimer's disease, Parkinson's disease, and restless legs syndrome.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Nutrition & Dietetics
Seok-Hui Kang, Bo-Yeon Kim, Eun-Jung Son, Gui-Ok Kim, Jun-Young Do
Summary: The aim of this study was to evaluate the survival rates of patients on maintenance hemodialysis (HD) according to their iron status. The study analyzed data from the National HD Quality Assessment Program and claims data (n = 42,390). The patients were divided into four groups based on their transferrin saturation rate and serum ferritin levels. The results showed that patients with normal iron status had the highest survival rates, while there were minimal differences in survival rates among the groups with abnormal iron status. Subgroup analyses based on age, hemoglobin, or serum albumin levels showed different trends.
Article
Biochemistry & Molecular Biology
Ewa Skarzynska, Monika Wrobel, Hanna Zborowska, Mateusz Franciszek Kolek, Grzegorz Manka, Mariusz Kiecka, Michal Lipa, Damian Warzecha, Robert Spaczynski, Piotr Piekarski, Beata Banaszewska, Artur Jakimiuk, Tadeusz Issat, Wojciech Rokita, Jakub Mlodawski, Maria Szubert, Piotr Sieroszewski, Grzegorz Raba, Kamil Szczupak, Tomasz Kluz, Marek Kluza, Miroslaw Wielgos, Barbara Lisowska-Myjak, Piotr Laudanski
Summary: The aim of this study was to investigate the relationship between lactoferrin and iron and its binding proteins in women with endometriosis. The results showed differences in lactoferrin, transferrin, ferritin, and iron levels between plasma and peritoneal fluid. Lactoferrin levels in plasma were associated with iron and transferrin in endometriosis, while lactoferrin in peritoneal fluid correlated with lactoferrin, iron, and transferrin in patients without endometriosis. The study suggests that assessing iron metabolism may be useful in diagnosing and monitoring endometriosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Bryan A. Killinger, Lee L. Marshall, Diptaman Chatterjee, Yaping Chu, Jose Bras, Rita Guerreiro, Jeffrey H. Kordower
Summary: This study used biotinylation by antibody recognition (BAR) to label pathological alpha-synuclein and performed mass spectrometry analysis on Lewy pathology (LP). It identified 261 enriched proteins in synucleinopathy brains and revealed PD as the most significant pathway. BAR has the potential to help understand LP in primary human tissue and animal models.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biochemistry & Molecular Biology
Matthias Eckhardt
Summary: Sphingolipids with hydroxylated acyl residues at C-2 are commonly found in eukaryotes and certain bacteria. These 2-hydroxylated sphingolipids are present in various organs and cell types, particularly in myelin and skin. The enzyme FA2H is responsible for the synthesis of many, but not all, 2-hydroxylated sphingolipids. Deficiency in FA2H leads to a neurodegenerative disease called hereditary spastic paraplegia 35 (HSP35/SPG35) or fatty acid hydroxylase-associated neurodegeneration (FAHN). Additionally, FA2H is implicated in other diseases, and its low expression level is associated with poor prognosis in many cancers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biology
Mengjiao Zhong, Bing Zhou
Summary: The study reveals the critical iron requirement of malaria parasites and the finely tuned iron homeostasis in these parasites, mediated by the newly identified iron importer PyDMT1. Tipping the iron balance between the parasite and host can efficiently kill the pathogenicity of the parasite.
Review
Biochemistry & Molecular Biology
M. T. Ciubuc-Batcu, N. J. C. Stapelberg, J. P. Headrick, G. M. C. Renshaw
Summary: The nervous system relies on mitochondria, and impaired mitochondrial function is associated with major depressive disorder. Modulating mitochondrial function may be a therapeutic target for treating MDD.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Correction
Biochemistry & Molecular Biology
Saowaluk Saisomboon, Ryusho Kariya, Piyanard Boonnate, Kanlayanee Sawanyawisuth, Ubon Cha'on, Vor Luvira, Yaovalux Chamgramol, Chawalit Pairojkul, Wunchana Seubwai, Atit Silsirivanit, Sopit Wongkham, Seiji Okada, Sarawut Jitrapakdee, Kulthida Vaeteewoottacharn
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Pavan Thapak, Zhe Ying, Victoria Palafox-Sanchez, Guanglin Zhang, Xia Yang, Fernando Gomez-Pinilla
Summary: Traumatic brain injury (TBI) impairs cellular energy demand, compromising neuronal function and plasticity. This study demonstrates that the mitochondrial activator humanin (HN) can counteract the reduction in mitochondrial bioenergetics caused by TBI, restore memory function and synaptic protein levels, and suppress inflammation and astrocyte proliferation. HN plays an integral role in normalizing fundamental aspects of TBI pathology.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
M. Paul Murphy, Valeria A. Buzinova, Carrie E. Johnson
Summary: Progress has been made in the treatment of Alzheimer's disease through the development of anti-A beta therapeutics, which have shown modest efficacy in slowing the progression of the disease. However, the puzzling issue remains as to why completely removing A beta does not fully stop the disease.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Review
Biochemistry & Molecular Biology
Yang Zhang, Mengqiu Hao, Xuyang Yang, Su Zhang, Junhong Han, Ziqiang Wang, Hai-Ning Chen
Summary: Colorectal cancer often requires adjuvant therapies to reduce tumor burden, and the efficacy of these therapies is significantly influenced by reactive oxygen species (ROS). ROS-mediated colorectal cancer adjuvant therapies involve multiple mechanisms, and preliminary clinical trials have shown the potential of ROS-manipulating therapy in enhancing treatment outcomes.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Mengxin Li, Xuanzhong Wang, Xuyang Chen, Jinghui Hong, Ye Du, Dong Song
Summary: Pancreatic adenocarcinoma (PAAD) is a common digestive malignant tumor with limited treatment options. This study demonstrates that TGM2 may serve as a marker for treatment and prognosis in pancreatic cancer patients. Co-treatment of low dose cisplatin (DDP) and the TGM2 inhibitor GK921 effectively inhibits PAAD cell viability and proliferation in vitro and in vivo, by inhibiting epithelial-to-mesenchymal transition (EMT) induced by TGM2 and enhancing cell cycle arrest and apoptosis caused by DDP. These findings suggest that the combination of GK921 and DDP holds promise as a treatment for PAAD patients.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Liaoran Niu, Qi Wang, Fan Feng, Wanli Yang, Zhenyu Xie, Gaozan Zheng, Wei Zhou, Lili Duan, Kunli Du, Yiding Li, Ye Tian, Junfeng Chen, Qibin Xie, Aqiang Fan, Hanjun Dan, Jinqiang Liu, Daiming Fan, Liu Hong, Jian Zhang, Jianyong Zheng
Summary: This review provides a comprehensive summary of the interaction between cancer cells and macrophages in the tumor microenvironment, and discusses the role of small extracellular vesicles (sEVs) in this process. It also explores the various effects of macrophage-secreted sEVs on tumor malignant transformation, and addresses the therapeutic advancements and challenges associated with these vesicles.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Neha Sawant, Sudhir Kshirsagar, P. Hemachandra Reddy, Arubala P. Reddy
Summary: Depression is a common neuropsychiatric comorbidity in Alzheimer's disease (AD) and other Tauopathies. Selective serotonin reuptake inhibitor (SSRI) treatment, such as Citalopram, not only has anti-depressive and anxiolytic effects, but also helps improve neurogenesis, reduce amyloid burden & Tau pathologies, and neuroinflammation in AD. In this study, Citalopram was found to reduce pathologically pTau level, increase synaptic gene expression and cytoskeletal structure, as well as improve cell survival, mitochondrial respiration, and mitochondrial morphology in cells expressing mutant APP and Tau. These findings suggest that Citalopram could be a promising therapeutic drug for treating depression and AD.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Yueqi Chen, Jiulin Tan, Chuan Yang, Zhiguo Ling, Jianzhong Xu, Dong Sun, Fei Luo
Summary: Bone is a self-healing organ that undergoes continuous regeneration through the cooperation of osteoclasts and osteoblasts. This study used ATAC-seq and RNA-Seq techniques to investigate the chromatin accessibility and transcriptomic landscape of osteoblast differentiation and mineralization. The results showed that global chromatin accessibility was extensively improved during osteoblastogenesis. Additionally, several transcription factors including MEF2A, PRRX1, Shox2, and HOXB13 were found to modulate the promoter accessibility of target genes during osteoblast differentiation.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Zi-Ran Kang, Shanshan Jiang, Ji-Xuan Han, Yaqi Gao, Yile Xie, Jinxian Chen, Qiang Liu, Jun Yu, Xin Zhao, Jie Hong, Haoyan Chen, Ying-Xuan Chen, Huimin Chen, Jing-Yuan Fang
Summary: The study demonstrates that BCAA metabolism is involved in the development of colorectal cancer (CRC). BCAT2 deficiency promotes CRC progression by inhibiting BCAA metabolism and chronically activating the mTORC1 pathway.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Chao Zheng, Lingling Liu, Caiyun Liu, Fengna Chu, Yue Lang, Shan Liu, Yan Mi, Jie Zhu, Tao Jin
Summary: Inducing tolerogenic dendritic cells (tDCs) with low RelB expression could effectively alleviate symptoms and reduce immune cell infiltration and demyelination in experimental autoimmune encephalomyelitis (EAE) mouse model.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Hang Lam Li, Simei Go, Jung-Chin Chang, Arthur Verhoeven, Ronald Oude Elferink
Summary: This review highlights the distinct characteristics and crucial role of soluble adenylyl cyclase (sAC) in cellular processes, as well as recent significant advancements in the field of sAC research.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
M. Seco-Cervera, D. Ortiz-Masia, D. C. Macias-Ceja, S. Coll, L. Gisbert-Ferrandiz, J. Cosin-Roger, C. Bauset, M. Ortega, B. Heras-Moran, F. Navarro-Vicente, M. Millan, J. V. Esplugues, S. Calatayud, M. D. Barrachina
Summary: The study revealed the presence of resistance to apoptosis in complicated ileal Crohn's disease, with PDGFB inducing an ETS1-mediated resistance to apoptosis associated with an inflammatory and fibrogenic pattern of expression in intestinal fibroblasts. Potential targets against ileal fibrosis include PDGFRB, IL1R1, or MCL1.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Review
Biochemistry & Molecular Biology
Yunmeng Wang, Ping Cheng
Summary: Oncolytic viruses (OVs) are emerging as therapeutically relevant anticancer agents, especially when combined with genetically modified bispecific T cell engagers (BiTEs). This combination strategy can overcome the limitations of BiTEs alone and provide targeted cytotoxicity to solid tumors.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Article
Biochemistry & Molecular Biology
Stephanie Tannous, Hassan Y. Naim
Summary: Congenital sucrase-isomaltase deficiency (CSID) is an autosomal recessive disorder caused by variants in the SI gene. A frameshift mutation called c.273_274delAG (p.Gly92Leufs*8) has been identified in CSID patients in Greenlandic population, which leads to loss of digestive function of SI. Surprisingly, the truncated mutant can still be located on the cell surface and interacts with wild type SI, negatively affecting its enzymatic function. Furthermore, heterozygote carriers of this mutation may also exhibit CSID symptoms.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)