Review
Clinical Neurology
Karthik Muthusamy, Ajith Sivadasan, Luke Dixon, Sniya Sudhakar, Maya Thomas, Sumita Danda, Zbigniew K. Wszolek, Klaas Wierenga, Radhika Dhamija, Ralitza Gavrilova
Summary: Adult-onset leukodystrophies, although individually rare, are not uncommon. They can be easily misdiagnosed due to the overlap with common acquired disorders and the challenges posed by non-specific white matter changes. A comprehensive evaluation and genetic confirmation are important for early diagnosis and treatment. In this review, we aim to provide a useful approach to adult-onset leukodystrophies, discussing their presentations, neuroimaging findings, treatment options, and diagnostic algorithms.
FRONTIERS IN NEUROLOGY
(2023)
Letter
Clinical Neurology
Luca Marsili, Marcelo A. Kauffman, Diandra Rufin Florat, Amir Zaidi, Vanesa Botsford, Jennifer Sharma, Elizabeth G. Keeling, Joseph P. Broderick, Saulius Sumanas, Alberto J. Espay
Summary: This article describes an elderly woman who meets the criteria for vascular parkinsonism/dementia associated with a likely pathogenic COL22A1 gene variant. The findings are supported by functional experiments in a zebrafish model. The authors suggest that white matter hyperintensities may not represent small-vessel ischemic disease and propose that COL22A1 may be included among the adult-onset leukoencephalopathies mislabeled as vascular parkinsonism.
PARKINSONISM & RELATED DISORDERS
(2023)
Review
Pharmacology & Pharmacy
Thomas Lee Moore, Giovanna Pannuzzo, Gabriella Costabile, Anna Lisa Palange, Raffaele Spano, Miguel Ferreira, Adriana Carol Eleonora Graziano, Paolo Decuzzi, Venera Cardile
Summary: Nanomedicines are being investigated as vehicles to deliver therapeutics into the brain for the treatment of rare neurodevelopmental disorders such as Krabbe disease. This article discusses the challenges and potential solutions for nanoparticle delivery to the brain, and emphasizes the impact it can have on treating various neurological disorders.
ADVANCED DRUG DELIVERY REVIEWS
(2023)
Review
Biochemistry & Molecular Biology
Rebecca Maechtel, Fanni Annamaria Boros, Jan Philipp Dobert, Philipp Arnold, Friederike Zunke
Summary: Lysosomes are acidic organelles responsible for recycling cellular components and can cause lysosomal dysfunction and LSDs when there is reduced enzymatic activity. Neurons are particularly susceptible to lysosomal dysfunction, leading to neurological symptoms. There are genetic associations between LSDs and Parkinson's disease, indicating common cellular mechanisms.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Genetics & Heredity
Martha Caterina Faraguna, Francesca Musto, Viola Crescitelli, Maria Iascone, Luigina Spaccini, Davide Tonduti, Tiziana Fedeli, Gaia Kullmann, Francesco Canonico, Alessandro Cattoni, Fabiola Dell'Acqua, Carmelo Rizzari, Serena Gasperini
Summary: MPS-PS is a rare genetic disorder characterized by various symptoms, and many patients die before the age of 1-2. Treatment with steroids may improve the patient's condition and quality of life, but further research is needed to confirm this.
Article
Neurosciences
Malabendu Jana, Debashis Dutta, Jit Poddar, Kalipada Pahan
Summary: In this study, gemfibrozil was found to alleviate disease pathology, reduce neuroinflammation, restore the level of TFEB, and decrease the accumulation of SCMAS in an animal model of JNCL. Gemfibrozil treatment also improved locomotor activities. These findings suggest that PPARa activation may be beneficial for JNCL and gemfibrozil may be repurposed for its treatment.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Endocrinology & Metabolism
Laura A. Adang, Samar Mowafy, Zackary M. Herbst, Zitao Zhou, Lars Schlotawa, Karthikeyan Radhakrishnan, Brenna Bentley, Vi Pham, Emily Yu, Nishitha R. Pillai, Paul J. Orchard, Mauricio De Castro, Adeline Vanderver, Marzia Pasquali, Michael H. Gelb, Rebecca C. Ahrens-Nicklas
Summary: This study evaluates residual sulfatase activity and GAG accumulation in multiple sulfatase deficiency (MSD) patients, and finds that different sulfatases have different tolerance to activation by formylglycine generating enzyme (FGE). Moreover, specific urinary GAG subspecies accumulation patterns can serve as biomarkers for disease severity. These findings provide important insights into sulfatase regulation and offer much-needed biomarkers for upcoming clinical trials.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Article
Clinical Neurology
Naoko Inamura, Shinji Go, Takashi Watanabe, Hiroshi Takase, Nobuyuki Takakura, Atsuo Nakayama, Hirohide Takebayashi, Junko Matsuda, Yasushi Enokido
Summary: Krabbe disease, caused by the deficiency of lysosomal galactosylceramidase activity, is a demyelinating disease with early-onset cerebral demyelination. The reduced expression of microRNA-219 in KD OLs plays a role in the pathogenesis of the disease, and miR-219 may have therapeutic potential for treating KD OL pathologies.
Article
Clinical Neurology
Xavier Ayrignac, Clarisse Carra-Dalliere, Pekes Codjia, Kevin Mouzat, Giovanni Castelnovo, Emmanuel Ellie, Frederique Etcharry-Bouyx, Serge Belliard, Cecilia Marelli, Florence Portet, Isabelle Le Ber, Francoise Durand-Dubief, Guillaume Mathey, Bruno Stankoff, Imen Dorboz, Severine Drunat, Odile Boespflug-Tanguy, Nicolas Menjot de Champfleur, Serge Lumbroso, Fanny Mochel, Pierre Labauge
Summary: The diagnostic criteria for ALSP have limited sensitivity and modest specificity overall, suggesting the need for a comprehensive approach including magnetic resonance imaging pattern-based analysis and genetic testing like white matter gene panel or whole exome sequencing in patients suspected of genetic leukoencephalopathy.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Nayibe Tatiana Sanchez-Alvarez, Paula Katherine Bautista-Nino, Juanita Trejos-Suarez, Norma Cecilia Serrano-Diaz
Summary: Metachromatic leukodystrophy is a neurological disease that affects public health. This research focuses on the use of metformin as a treatment to counteract the effects of enzyme deficiencies and sulfatide accumulation. The study found that transfected human Schwann cells showed increased cell reactive oxygen species production when exposed to sulfatides, and sulfatides affected mitochondrial bioenergetics in these cells. Treatment with metformin restored the metabolic activity of the cells and decreased ROS production.
Article
Biochemistry & Molecular Biology
Leanne K. Winner, Helen Beard, Litsa Karageorgos, Nicholas J. Smith, John J. Hopwood, Kim M. Hemsley
Summary: Acute neuronopathic Gaucher disease is a devastating neurological disorder caused by mutations in the glucocerebrosidase gene, leading to the accumulation of specific lipids. In this study, the pathological changes in GD lamb brain were examined and compared to those in GD patient tissue, confirming the validity of the ovine model.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Review
Biochemistry & Molecular Biology
Hiu Chuen Lok, John B. Kwok
Summary: Frontotemporal dementia (FTD) is a common cause of presenile dementia characterized by behavioral and/or language changes and progressive cognitive deficits. Genetics plays a significant role in the etiology of FTD, with a reported positive family history of dementia in 40% of cases. The review emphasizes the importance of common variants and mutations in genes related to microglia and oligodendrocyte function, and discusses potential pharmacological and non-pharmacological approaches for enhancing remyelination in future FTD treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Allison M. Bradbury, Ernesto R. Bongarzone, Mark S. Sands
Summary: Krabbe disease is a lysosomal storage disease characterized by demyelination, most commonly in its infantile form. It is caused by a deficiency of the acid hydrolase galactosylceramidase (GALC). Hematopoietic stem cell transplantation can slow the progression of the disease, but more effective treatments are still needed to combat this devastating condition.
NEUROSCIENCE LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Katharina B. Kuentzel, Ivan Bradic, Alena Akhmetshina, Melanie Korbelius, Silvia Rainer, Dagmar Kolb, Martin Gauster, Nemanja Vujic, Dagmar Kratky
Summary: The research showed that defective lysosomal CE catabolism affects placental and fetal cholesterol homeostasis, leading to hepatic lysosomal lipid accumulation in Lal-/- fetuses. After birth, LAL deficiency worsens with massive hepatic lysosomal lipid accumulation, continuing to deteriorate into young adulthood.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Editorial Material
Cell Biology
Jerry Schneider, Elena Levtchenko
Summary: This article describes the remarkable contributions of Dr. Jerry Schneider, an American physician and scientist, in the field of cystinosis research. Starting from his seminal Science paper, Dr. Schneider led a research team in understanding the pathogenesis of cystinosis and finding treatments for this devastating disease. His personal history highlighted the major milestones in cystinosis research, serving as an inspiration and guide for young doctors and scientists continuing the quest for a cure.
