Immunoglobulin gamma (IgG) heavy chain genes are associated with susceptibility to multiple sclerosis (MS) and IgG levels in the cerebrospinal fluid (CSF). However, how these variants are implicated in disease mechanisms remains unknown. Here, we show that proliferating plasmablasts expressing the G1m1 allotype of IgG1 are selectively enriched in CSF of G1m1/G1m3 heterozygous MS patients, whereas plasmablasts expressing either G1m1 or G1m3 are evenly distributed in blood. Moreover, there was a preferential intrathecal synthesis of oligoclonal IgG1 of the G1m1 allotype in heterozygous patients, whereas controls with Lyme neuroborreliosis displayed oligoclonal IgG1 of both allotypes. This points to a disease-specific mechanism involved in B-cell establishment within the central nervous system in MS.
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http://dx.doi.org/10.1002/acn3.451 | DOI Listing |
Sci Rep
January 2025
Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, J5, 68159, Mannheim, Germany.
Inflammatory processes have been implicated in the pathophysiology of depression. In human studies, inflammation has been shown to act as a critical disease modifier, promoting susceptibility to depression and modulating specific endophenotypes of depression. However, there is scant documentation of how inflammatory processes are associated with neural activity in patients with depression.
View Article and Find Full Text PDFJ Neurol Sci
January 2025
Brigham MS Center, Brigham and Women's Hospital, Boston, MA, United States of America; Department of Neurology, Harvard Medical School, Boston, MA, United States of America. Electronic address:
Background: Cognitive impairment occurs frequently in persons with multiple sclerosis (PwMS) at some point in the course of the disease. However, not all PwMS develop cognitive difficulties suggesting a role for important moderating factors. We examined baseline predictors of cross-sectional and longitudinal change in cognitive performance in PwMS.
View Article and Find Full Text PDFMult Scler Relat Disord
December 2024
IRCCS Fondazione Don Carlo Gnocchi ONLUS, Milan, Italy. Electronic address:
Background: Multiple sclerosis (MS) is a demyelinating disease characterized by balance and gait impairment, fatigue, anxiety, depression, and diminished quality of life. Transcranial direct current stimulation (tDCS) has emerged as an effective intervention for managing these symptoms.
Objective: This study aims to investigate the efficacy of remotely supervised tDCS (RS-tDCS) applied to the left dorsolateral prefrontal cortex, in conjunction with a telerehabilitation (TR) program, on motor (balance and gait), cognitive (executive functions), and participation outcomes (fatigue, anxiety, depression, and quality of life) in persons with MS (pwMS).
J Biochem Mol Toxicol
January 2025
Department of Medical Biochemistry, Faculty of Medicine, Kahramanmaraş Sütçü İmam University, Kahramanmaraş, Turkey.
Neurodegenerative diseases are significant health concerns that have a profound impact on the quality and duration of life for millions of individuals. These diseases are characterized by pathological changes in various brain regions, specific genetic mutations associated with the disease, deposits of abnormal proteins, and the degeneration of neurological cells. As neurodegenerative disorders vary in their epidemiological characteristics and vulnerability of neurons, treatment of these diseases is usually aimed at slowing disease progression.
View Article and Find Full Text PDFMol Ther
January 2025
Program of Cellular and Molecular Biology, Biomedical Sciences Institute (ICBM), Universidad de Chile, Santiago, Chile; Biomedical Neuroscience, Faculty of Medicine, Universidad de Chile, Santiago, Chile; FONDAP Center for Geroscience, Brain Health and Metabolism, Santiago, Chile; Buck Institute for Research on Aging, Novato, CA, USA. Electronic address:
Amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia (FTD) are part of a spectrum of diseases that share several causative genes, resulting in a combinatory of motor and cognitive symptoms and abnormal protein aggregation. Multiple unbiased studies have revealed that proteostasis impairment at the level of the endoplasmic reticulum (ER) is a transversal pathogenic feature of ALS/FTD. The transcription factor XBP1s is a master regulator of the unfolded protein response (UPR), the main adaptive pathway to cope with ER stress.
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