Article
Neurosciences
Rachel M. Wise, Annika Wagener, Urban M. Fietzek, Thomas Klopstock, Eugene V. Mosharov, Fabio A. Zucca, David Sulzer, Luigi Zecca, Lena F. Burbulla
Summary: The involvement of dopamine metabolism, alpha-synuclein pathology, and iron homeostasis has been implicated in the unique vulnerability of substantia nigra dopaminergic neurons. However, the mechanisms contributing to disease progression and resulting in dopaminergic neuron loss are still not completely understood. The disrupted interplay of dopamine, alpha-synuclein, and iron pathways may synergize to promote pathology and drive vulnerability to disease states.
NEUROBIOLOGY OF DISEASE
(2022)
Review
Cell Biology
Irene Villalon-Garcia, Suleva Povea-Cabello, Monica Alvarez-Cordoba, Marta Talaveron-Rey, Juan M. Suarez-Rivero, Alejandra Suarez-Carrillo, Manuel Munuera-Cabeza, Diana Reche-Lopez, Paula Cilleros-Holgado, Rocio Pinero-Perez, Jose A. Sanchez-Alcazar
Summary: Lipid peroxidation and iron accumulation are closely linked to neurodegenerative diseases, and understanding their mechanisms is essential for developing therapeutic strategies. This review explores the connection between lipid peroxidation and iron accumulation in neurodegeneration, including the role of mitochondrial dysfunction, lipofuscin accumulation, autophagy disruption, and ferroptosis. The vicious cycle established between these pathological alterations may contribute to the development of neurodegeneration.
NEURAL REGENERATION RESEARCH
(2023)
Article
Genetics & Heredity
Vasco Sousa Abreu, Jose Sa Silva, Liliana Igreja, Maria Joao Malaquias, Catarina Mendes Pinto
Summary: The eye-of-the-tiger sign is a bilateral and symmetrical change in the globus pallidus, which can be associated with various neurodegenerative or genetic diseases, including CANVAS, which has been linked to repeat expansion in the RFC1 gene.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Clinical Neurology
Elahe Amini, Mohammad Rohani, Alfonso Fasano, Zahra Azad, Shahnaz Miri, Seyed Amir Hassan Habibi, Maziar Emamikhah, Reza Mirshahi, Mohammad Taghi Joghataei, Zeinab Gholibeigian, Khalil Ghasemi Falavarjani
Summary: Observing pathological structural and functional neurovascular changes in NBIA patients may provide an opportunity to elucidate the underlying mechanisms and differential retinal biomarkers in NBIA subtypes.
MOVEMENT DISORDERS
(2023)
Article
Neurosciences
Alaa Abdelgawad, Shady Rahayel, Ying-Qiu Zheng, Christina Tremblay, Andrew Vo, Bratislav Misic, Alain Dagher
Summary: This study presents a model that simulates the progression of brain atrophy in Parkinson's disease by mimicking the movement of normal and abnormal alpha-synuclein molecules in the brain network. The authors conclude that the pattern of brain atrophy in Parkinson's disease is influenced by the connectome and regional expression of genes related to alpha-synuclein synthesis and clearance. This research supports the prion-like model of neurodegeneration in Parkinson's disease.
NETWORK NEUROSCIENCE
(2023)
Review
Chemistry, Medicinal
Indira Y. Rao, Leah R. Hanson, Julia C. Johnson, Michael H. Rosenbloom, William H. Frey
Summary: This study aims to examine the relationship between glucose hypometabolism (GHM) and brain iron accumulation (BIA) in different regions of the brain in late-onset Alzheimer's disease (AD) or Parkinson's disease (PD) patients. The findings suggest that GHM and BIA exist independently in various brain regions in both AD and PD, indicating that they may not always be necessary or sufficient to cause each other.
Review
Clinical Neurology
Vassilena Iankova, Ivan Karin, Thomas Klopstock, Susanne A. Schneider
Summary: NBIA is a group of heterogeneous neurodegenerative diseases characterized by iron accumulation in the globus pallidus and substantia nigra. The four most common forms include PKAN, PLA2G6, BPAN, and MPAN, presenting with a wide range of clinical symptoms. Treatment remains symptomatic with iron chelators being a common mechanistic approach.
FRONTIERS IN NEUROLOGY
(2021)
Article
Multidisciplinary Sciences
Tz-Yun Jan, Lee-Chin Wong, Ming-Tao Yang, Chien-Feng Judith Huang, Chia-Jui Hsu, Steven Shinn-Forng Peng, Wen-Yih Isaac Tseng, Wang-Tso Lee
Summary: Individuals with Rett syndrome commonly exhibit Parkinsonian features and dystonia during their teenage years, with abnormal iron accumulation in deep gray matter. Age showed moderate to high negative correlations with iron accumulation, while dystonia scales were correlated with iron accumulation in dopaminergic system and related grey matter. This study suggests that increased iron deposition may partly explain the gradually increased dystonia in Rett syndrome patients.
SCIENTIFIC REPORTS
(2021)
Article
Genetics & Heredity
Renata Toth-Bencsik, Peter Balicza, Edina Timea Varga, Andras Lengyel, Gabor Rudas, Aniko Gal, Maria Judit Molnar
Summary: This study investigated the clinical symptoms, genetic mutations, and neuroimaging data of a family affected by Phospholipase A2-associated Neurodegeneration (PLAN). Despite the distinct age-related phenotypes in PLAN, the disease is not strict categories but rather a continuous phenotypic spectrum. The study suggests that even heterozygous pathogenic variants might be associated with clinical symptoms in some cases.
FRONTIERS IN GENETICS
(2021)
Article
Biochemistry & Molecular Biology
Jin Xue, Yingbao Zhu, Liyi Wei, Hongjing Huang, Guangxu Li, Wen Huang, Hua Zhu, Ranhui Duan
Summary: NgBR, encoded by NUS1 gene, is involved in cholesterol transport and the risk of Parkinson's disease. Knockdown of tango14, the ortholog of NUS1, in fruit flies leads to decreased locomotive abilities, loss of dopaminergic neurons, and cholesterol accumulation. This study also reveals neurodegenerative effects and increased alpha-synuclein neurotoxicity in tango14 knockdown flies.
Article
Clinical Neurology
Guangwei Du, Ernest Wang, Christopher Sica, Hairong Chen, Sol De Jesus, Mechelle M. Lewis, Lan Kong, James Connor, Richard B. Mailman, Xuemei Huang
Summary: Higher nigral iron has been reported in Parkinson's disease (PD) patients. Nigral iron is lower before the start of dopaminergic medication and then increases throughout the disease until it plateaus at late stages. PD medications may have differential associations with iron accumulation that need further investigation.
MOVEMENT DISORDERS
(2022)
Article
Geriatrics & Gerontology
Dongling Zhang, Junye Yao, Junyan Sun, Junling Wang, Lili Chen, Hongjian He, Tao Wu
Summary: This study aimed to quantitatively evaluate iron content in the VTA across different stages of PD in order to help explain the selective loss of dopamine neurons in PD. The results showed that there is no increased iron accumulation in the VTA during the prodromal and early clinical stages of PD, but iron deposition increases significantly as the disease becomes more severe.
FRONTIERS IN AGING NEUROSCIENCE
(2023)
Article
Pediatrics
Prajnya Ranganath, Mallikarjun Patil
Summary: The study reports a patient with fucosidosis who had MRI brain findings closely resembling the eye-of-the-tiger sign.
JOURNAL OF PEDIATRIC GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Luisa Aring, Eun-Kyung Choi, Huira Kopera, Thomas Lanigan, Shigeki Iwase, Daniel J. Klionsky, Young Ah Seo
Summary: Neurodegeneration with brain iron accumulation (NBIA) is a group of neurodegenerative diseases characterized by abnormal brain iron accumulation and progressive degeneration of the nervous system. Beta-propeller protein-associated neurodegeneration (BPAN) is a recently identified subtype caused by mutations in the WDR45/WIPI4 gene. Research has shown that deficiency of WDR45 leads to iron accumulation in cells and affects cellular functions.
JOURNAL OF NEUROCHEMISTRY
(2022)
Article
Medicine, General & Internal
Nicola Romano, Giammarco Baiardi, Valeria Maria Pinto, Sabrina Quintino, Barbara Gianesin, Riccardo Sasso, Andrea Diociasi, Francesca Mattioli, Roberta Marchese, Giovanni Abbruzzese, Antonio Castaldi, Gian Luca Forni
Summary: Neurodegeneration with brain iron accumulation (NBIA) is a group of rare diseases characterized by brain iron overload. Current treatment options only focus on symptom management. The use of deferiprone (DFP) appears to be a promising strategy for reducing iron accumulation and improving clinical symptoms.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Clinical Neurology
Ghil Schwarz, Gargi Banerjee, Isabel C. Hostettler, Gareth Ambler, David J. Seiffge, Hatice Ozkan, Simone Browning, Robert Simister, Duncan Wilson, Hannah Cohen, Tarek Yousry, Rustam Al-Shahi Salman, Gregory Y. H. Lip, Martin M. Brown, Keith W. Muir, Henry Houlden, Rolf Jager, David J. Werring
Summary: This study found associations between putative biomarkers of parenchymal CAA and putative biomarkers of leptomeningeal CAA, and suggested that CT biomarkers may help in diagnosing CAA, but MRI still plays an important role in ICH survivors with suspected CAA.
INTERNATIONAL JOURNAL OF STROKE
(2023)
Review
Clinical Neurology
Francesca Magrinelli, Kailash P. Bhatia, Mehran Beiraghi Toosi, Fatemeh Arab, Ehsan Ghayoor Karimiani, Sahar Sedighzadeh, Behnaz Ansari, Maedeh Neshatdoust, Clarissa Rocca, Henry Houlden, Reza Maroofian
Summary: This article reports a new phenotype of childhood-onset choreo-dystonia in four patients from two unrelated Iranian pedigrees, who harbor a novel pathogenic variant in the HPCA gene. A systematic review of the literature reveals that HPCA-related dystonia can present as an isolated condition or in combination with various symptoms. Most cases show a poor or no response to common antidystonic medications.
MOVEMENT DISORDERS CLINICAL PRACTICE
(2023)
Article
Clinical Neurology
Vincenzo Salpietro, Valentina Galassi Deforie, Stephanie Efthymiou, Emer O'Connor, Anna Marce-Grau, Reza Maroofian, Pasquale Striano, Federico Zara, Michelle M. Morrow, Adi Reich, Amy Blevins, Julia Sala-Coromina, Andrea Accogli, Sara Fortuna, Marie Alesandrini, P. Y. Billie Au, Nilika Shah Singhal, Benjamin Cogne, Bertrand Isidor, Michael G. Hanna, Alfons Macaya, Dimitri M. Kullmann, Henry Houlden, Roope Mannikko
Summary: Novel mutations in KCNA6 gene were found to be associated with early infantile epileptic phenotypes and neurodevelopmental anomalies. Functional characterization revealed that these mutations affect channel closure and voltage dependence. This study is the first to report the association between de novo variants in KCNA6 and neurological features.
Article
Clinical Neurology
Ben Gaastra, Poppy Duncan, Mark K. Bakker, Isabel C. Hostettler, Varinder S. Alg, Henry Houlden, Ynte M. Ruigrok, Ian Galea, Will Tapper, David Werring, Diederik Bulters
Summary: This study found that genetic variation in nuclear factor erythroid 2-related factor 2 (NRF2) is associated with clinical outcome following aneurysmal subarachnoid haemorrhage (aSAH), indicating a clinically relevant pathophysiological role for oxidative and inflammatory brain injury in aSAH. The findings also suggest NRF2 as a potential therapeutic target for aSAH and other forms of intracranial haemorrhage.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Genetics & Heredity
Elisa Cali, Mohnish Suri, Marcello Scala, Matteo P. Ferla, Shahryar Alavi, Eissa Ali Faqeih, Emilia K. Bijlsma, Kristen M. Wigby, Diana Baralle, Mohammad Y. Mehrjardi, Jennifer Schwab, Konrad Platzer, Katharina Steindl, Mais Hashem, Marilyn Jones, Dmitriy M. Niyazov, Jennifer Jacober, Rebecca Okashah Littlejohn, Denisa Weis, Neda Zadeh, Lance Rodan, Alice Goldenberg, Francois Lecoquierre, Marina Dutra-Clarke, Gabriella Horvath, Dana Young, Naama Orenstein, Shahad Bawazeer, Anneke T. Vulto-van Silfhout, Yvan Herenger, Mohammadreza Dehghani, Seyed Mohammad Seyedhassani, Amir Bahreini, Mahya E. Nasab, A. Gulhan Ercan-Sencicek, Zahra Firoozfar, Mojtaba Movahedinia, Stephanie Efthymiou, Pasquale Striano, Ehsan Ghayoor Karimiani, Vincenzo Salpietro, Jenny C. Taylor, Melody Redman, Alexander P. A. Stegmann, Andreas Laner, Ghada Abdel-Salam, Megan Li, Mario Bengala, Amelie Johanna Muller, Maria C. Digilio, Anita Rauch, Murat Gunel, Hannah Titheradge, Daniela N. Schweitzer, Alison Kraus, Irene Valenzuela, Scott D. McLean, Chanika Phornphutkul, Mustafa Salih, Amber Begtrup, Rhonda E. Schnur, Erin Torti, Tobias B. Haack, Carlos E. Prada, Fowzan S. Alkuraya, Henry Houlden, Reza Maroofian
Summary: PRMT7-related syndrome is a neurodevelopmental disorder characterized by short stature, intellectual developmental disability, hypotonia, brachydactyly, and distinct facial morphology. This study provides a comprehensive description of the clinical characteristics of this syndrome, contributing to a better understanding of the disease.
GENETICS IN MEDICINE
(2023)
Article
Genetics & Heredity
Heba Morsy, Mehdi Benkirane, Elisa Cali, Clarissa Rocca, Kristina Zhelcheska, Valentina Cipriani, Evangelia Galanaki, Reza Maroofian, Stephanie Efthymiou, David Murphy, Mary O'Driscoll, Mohnish Suri, Siddharth Banka, Jill Clayton-Smith, Thomas Wright, Melody Redman, Jennifer A. Bassetti, Mathilde Nizon, Benjamin Cogne, Rami Abu Jamra, Tobias Bartolomaeus, Marion Heruth, Ilona Krey, Janina Gburek-Augustat, Dagmar Wieczorek, Felix Gattermann, Meriel Mcentagart, Alice Goldenberg, Lucie Guyant-Marechal, Hector Garcia-Moreno, Paola Giunti, Brigitte Chabrol, Severine Bacrot, Roger Buissonniere, Virginie Magry, Vykuntaraju K. Gowda, Varunvenkat M. Srinivasan, Bela Melegh, Andras Szabo, Katalin Sumegi, Mireille Cossee, Monica Ziff, Russell Butterfield, David Hunt, Georgina Bird-Lieberman, Michael Hanna, Michel Koenig, Michael Stankewich, Jana Vandrovcova, Henry Houlden
Summary: The purpose of this study was to understand the phenotypic spectrum of SPTAN1 variants. It was found that SPTAN1 variants were significantly enriched in families with hereditary ataxia or hereditary spastic paraplegia. A total of 31 individuals with SPTAN1 variants were identified, with 10 patients presenting with pure or complex HSP/HA and the remaining 21 patients having developmental delay and seizures. Fibroblasts derived from two patients showed irregular alpha II-spectrin aggregation.
GENETICS IN MEDICINE
(2023)
Article
Genetics & Heredity
Ella F. Whittle, Madison Chilian, Ehsan Ghayoor Karimiani, Helga Progri, Daniela Buhas, Melis Kose, Rebecca D. Ganetzky, Mehran Beiraghi Toosi, Paria Najarzadeh Torbati, Reza Shervin Badv, Ivan Shelihan, Hui Yang, Houda Zghal Elloumi, Sukyeong Lee, Yalda Jamshidi, Alan M. Pittman, Henry Houlden, Erika Ignatius, Shamima Rahman, Reza Maroofian, Wan Hee Yoon, Christopher J. Carrol
Summary: This study aimed to identify the genetic cause of a novel autosomal recessive neurodevelopmental disorder characterized by global developmental delay, movement disorder, and metabolic abnormalities. Through clinical characterization and genetic analysis, the researchers identified three novel homozygous variants in the OGDH gene. Functional studies demonstrated that these variants interfered with the structure and function of the OGDH protein, leading to the observed neurodevelopmental disorder. This research highlights the importance of studying genetic causes of neurodevelopmental disorders for understanding their underlying mechanisms and developing targeted therapies.
GENETICS IN MEDICINE
(2023)
Article
Neurosciences
Jingzhang Wei, Charles Arber, Selina Wray, John Hardy, Thomas M. M. Piers, Jennifer M. M. Pocock
Summary: One type of early life stress, prenatal exposure to glucocorticoids (GCs), increases the risk of psychiatric and neurodevelopmental disorders in later life. Microglial cells are being increasingly recognized for their importance in these disorders. However, research on GCs exposure during microglial development is limited, especially in human studies. In this study, an in vitro model of early life stress was established by pre-exposing human iPS-microglia to GCs during primitive hematopoiesis, and the effects on microglial phenotype were examined. The findings suggest that prolonged GCs exposure during primitive hematopoiesis leads to changes in the matured iPS-microglia, potentially contributing to ELS-associated disorders.
Article
Neurosciences
Zhongbo Chen, Regina H. Reynolds, Antonio F. Pardinas, Sarah A. Gagliano Taliun, Wouter van Rheenen, Kuang Lin, Aleksey Shatunov, Emil K. Gustavsson, Isabella Fogh, Ashley R. Jones, Wim Robberecht, Philippe Corcia, Adriano Chio, Pamela J. Shaw, Karen E. Morrison, Jan H. Veldink, Leonard H. van den Berg, Christopher E. Shaw, John F. Powell, Vincenzo Silani, John A. Hardy, Henry Houlden, Michael J. Owen, Martin R. Turner, Mina Ryten, Ammar Al-Chalabi
Summary: This study found that Neanderthal DNA introgression does not contribute to the genetic risk of neurodegenerative disorders in anatomically-modern humans. Additionally, there is no evidence to support the idea that common variants associated with these disorders are maintained by natural selection. These findings provide valuable insights into the origins of neurodegenerative diseases and address longstanding debates.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Multidisciplinary Sciences
Karishma D'Sa, Sebastian Guelfi, Jana Vandrovcova, Regina H. Reynolds, David Zhang, John Hardy, Juan A. Botia, Michael E. Weale, Sarah A. Gagliano Taliun, Kerrin S. Small, Mina Ryten
Summary: This study revealed that the genetic regulation of gene expression mainly occurs post-transcriptionally in the cytoplasm, with synaptic genes more likely to undergo this form of regulation. These findings are crucial for understanding the structure of gene expression regulation in the human brain and interpreting large-scale gene association studies.
SCIENTIFIC REPORTS
(2023)
Editorial Material
Biochemistry & Molecular Biology
Benjamin O'Callaghan, John Hardy, Helene Plun-Favreau
Summary: The genetics of Parkinson's disease has played a crucial role in understanding the PINK1-dependent mitophagy process. In this article, we examine the implications of a 2010 PLOS Biology paper that provided insight into the functional significance of PINK1 in the mitophagy cascade.
Article
Genetics & Heredity
Nurlan Kerimov, Ralf Tambets, James D. Hayhurst, Ida Rahu, Peep Kolberg, Uku Raudvere, Ivan Kuzmin, Anshika Chowdhary, Andreas Vija, Hans J. Teras, Masahiro Kanai, Jacob Ulirsch, Mina Ryten, John Hardy, Sebastian Guelfi, Daniah Trabzuni, Sarah Kim-Hellmuth, William Rayner, Hilary Finucane, Hedi Peterson, Abayomi Mosaku, Helen Parkinson, Kaur Alasoo
Summary: The eQTL Catalogue is an open database of uniformly processed human molecular quantitative trait loci (QTLs) that has been continuously updated to improve its utility in interpreting genetic associations with complex traits. The updates include an increase in the number of studies and datasets covered, implementation of statistical fine mapping, and development of static QTL coverage plots. These updates have been demonstrated to be useful in interpreting genetic variants associated with vitamin D levels in human plasma and will facilitate the interpretation of complex trait associations identified by other human genetics efforts.
Letter
Clinical Neurology
John Hardy
BRAIN COMMUNICATIONS
(2023)
Review
Clinical Neurology
Yee Yen Goh, Emma Saunders, Samantha Pavey, Emma Rushton, Niall Quinn, Henry Houlden, Viorica Chelban
Summary: This article is a practical guide to diagnosing and managing multiple system atrophy (MSA). It explains the newly published Movement Disorders Society Consensus Diagnostic Criteria, which aim to reduce time to diagnosis. The key clinical features of MSA are highlighted to aid in diagnosis. The article also discusses practical symptom management and improving quality of life for people with MSA.
PRACTICAL NEUROLOGY
(2023)
Article
Clinical Neurology
Connor Langworth-Green, Saisha Patel, Zane Jaunmuktane, Edwin Jabbari, Huw Morris, Maria Thom, Andrew Lees, John Hardy, Michael Zandi, Karen Duff
Summary: Tauopathies are neurodegenerative disorders characterized by the aggregation of tau protein. Chronic inflammation plays a significant role in the pathogenesis of Alzheimer's disease, but its effects on tau pathology have been overlooked. Factors such as infection, brain injury, seizures, and autoimmune disease can trigger tau pathology through inflammatory processes. Understanding the chronic effects of inflammation on tauopathies may lead to the development of immunomodulatory interventions for clinical use.