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Gut dysbiosis was inevitable, but tolerance was not: temporal responses of the murine microbiota that maintain its capacity for butyrate production correlate with sustained antinociception to chronic morphine.
Gut Microbes
December 2025
Department of Molecular, Cellular, & Biomedical Sciences, University of New Hampshire, Durham, NH, USA.
The therapeutic benefits of opioids are compromised by the development of analgesic tolerance, which necessitates higher dosing for pain management thereby increasing the liability for drug dependence and addiction. Rodent models indicate opposing roles of the gut microbiota in tolerance: morphine-induced gut dysbiosis exacerbates tolerance, whereas probiotics ameliorate tolerance. Not all individuals develop tolerance, which could be influenced by differences in microbiota, and yet no study design has capitalized upon this natural variation.
View Article and Find Full Text PDFPoint of view: Challenges in implementation of new immunotherapies for Alzheimer's disease.
J Prev Alzheimers Dis
January 2025
Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, BioClinicum, 171 64 Solna, Sweden; Theme Inflammation and Aging, Karolinska University Hospital, 141 86 Stockholm, Sweden.
The advancement of disease-modifying treatments (DMTs) for Alzheimer's disease (AD), along with the approval of three amyloid-targeting therapies in the US and several other countries, represents a significant development in the treatment landscape, offering new hope for addressing this once untreatable chronic progressive disease. However, significant challenges persist that could impede the successful integration of this class of drugs into clinical practice. These challenges include determining patient eligibility, appropriate use of diagnostic tools and genetic testing in patient care pathways, effective detection and monitoring of side effects, and improving the healthcare system's readiness by engaging both primary care and dementia specialists.
View Article and Find Full Text PDFBlarcamesine for the treatment of Early Alzheimer's Disease: Results from the ANAVEX2-73-AD-004 Phase IIB/III trial.
J Prev Alzheimers Dis
January 2025
Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA. Electronic address:
Background: There are no approved oral disease-modifying treatments for Alzheimer's disease (AD).
Objectives: The objective of this study was to assess efficacy and safety of blarcamesine (ANAVEX®2-73), an orally available small-molecule activator of the sigma-1 receptor (SIGMAR1) in early AD through restoration of cellular homeostasis including autophagy enhancement.
Design: ANAVEX2-73-AD-004 was a randomized, double-blind, placebo-controlled, 48-week Phase IIb/III trial.
Marchiafava-Bignami disease post-bariatric surgery: A case report and review of similar cases.
Neurosciences (Riyadh)
January 2025
From the Neurology of Unit, Department of Medicine, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia.
Marchiafava-Bignami disease (MBD) is a rare neurological disorder typically occurring in alcoholic patients. The main disease mechanism is hypothesized to be vitamin B-complex deficiency due to malnutrition. In the literature, there have been few reported cases of the disease occurring in patients who have undergone bariatric surgery.
View Article and Find Full Text PDFGut microbiota in Alzheimer's disease: understanding molecular pathways and potential therapeutic perspectives.
Ageing Res Rev
January 2025
i+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), 47012 Valladolid, Spain; Physical Activity and Health Research Group (PaHerg), Research Institute of the Hospital 12 de Octubre ('imas12'), 28041 Madrid, Spain. Electronic address:
Accumulating evidence suggests that gut microbiota (GM) plays a crucial role in Alzheimer's disease (AD) pathogenesis and progression. This narrative review explores the complex interplay between GM, the immune system, and the central nervous system in AD. We discuss mechanisms through which GM dysbiosis can compromise intestinal barrier integrity, enabling pro-inflammatory molecules and metabolites to enter systemic circulation and the brain, potentially contributing to AD hallmarks.
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