Alzheimer's disease (AD) is an irreversible and progressive neurodegenerative disorder. Most existing treatments only provide symptomatic solutions. Here, we introduce currently available commercial drugs and new therapeutics, including repositioned drugs, to treat AD. Despite tremendous efforts, treatments targeting the hallmarks of AD show limited efficacy. Challenges in treating AD are partly caused by difficulties in penetrating the blood-brain barrier (BBB). Recently, nanoparticle (NP)-based systems have shown promising potential as precision medicines that can effectively penetrate the BBB and enhance the targeting ability of numerous drugs. Here, we describe how NPs enter the brain by crossing, avoiding, or disrupting the BBB. In addition, we provide an overview of the action of NPs in the microenvironment of the brain for the treatment of AD. Diverse systems, including liposomes, micelles, polymeric NPs, solid-lipid NPs, and inorganic NPs, have been investigated for NP drug loading to relieve AD symptoms, target AD hallmarks, and target moieties to diagnose AD. We also highlight NP-based immunotherapy, which has recently gained special attention as a potential treatment option to disrupt AD progression. Overall, this review focuses on recently investigated NP systems that represent innovative strategies to understand AD pathogenesis and suggests treatment and diagnostic modalities to cure AD.
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http://dx.doi.org/10.3390/pharmaceutics14040835 | DOI Listing |
PLoS One
January 2025
King's College London-Institute of Psychiatry, Psychology & Neuroscience, London, United Kingdom.
Major depressive disorder (MDD) is defined by an array of symptoms that make it challenging to understand the condition at a population level. Subtyping offers a way to unpick this phenotypic diversity for improved disorder characterisation. We aimed to identify depression subtypes longitudinally using the Inventory of Depressive Symptomatology: Self-Report (IDS-SR).
View Article and Find Full Text PDFMetab Brain Dis
January 2025
Department of Biochemistry, Faculty of Science, University of Yaoundé 1, P.O. Box 812, Yaounde, Cameroon.
Alzheimer's disease (AD) is associated with cognitive impairments which are linked to a deficit in cholinergic function. The objective of this study was to evaluate the ability of TeMac™ to prevent memory impairment in scopolamine-rats model of Alzheimer's disease and by in silico approaches to identify molecules in TeMac™ inhibiting acetylcholinesterase. The cholinergic cognitive dysfunction was induced by intraperitoneal injection of scopolamine (1 mg/kg daily) in male Wistar rats for seven consecutive days.
View Article and Find Full Text PDFMetab Brain Dis
January 2025
Department of Neurology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA.
Neuroinflammation and mitochondrial dysfunction are early events in Alzheimer's disease (AD) and contribute to neurodegeneration and cognitive impairment. Evidence suggests that the inflammatory axis mediated by macrophage migration inhibitory factor (MIF) binding to its receptor, CD74, plays an important role in many central nervous system (CNS) disorders such as AD. Our group has developed DRhQ, a novel CD74 binding construct which competitively inhibits MIF binding, blocks macrophage activation and migration into the CNS, enhances anti-inflammatory microglia cell numbers and reduces pro-inflammatory gene expression.
View Article and Find Full Text PDFInflammopharmacology
January 2025
Department of Pharmacology, Central University of Punjab, Bathinda, 151001, Punjab, India.
Alzheimer's Disease (AD), a progressive and age-associated neurodegenerative disorder, is primarily characterized by amyloid-beta (Aβ) plaques and neurofibrillary tangles. Despite advances in targeting Aβ-mediated neuronal damage with anti-Aβ antibodies, these treatments provide only symptomatic relief and fail to address the multifactorial pathology of the disease. This necessitates the exploration of novel therapeutic approaches and a deeper understanding of molecular signaling mechanisms underlying AD.
View Article and Find Full Text PDFAlzheimers Dement
January 2025
Institute for Biomedical Engineering and Institute of Pharmacology and Toxicology, Faculty of Medicine, University of Zurich, Zurich, Switzerland.
Introduction: Transcranial pulse stimulation (TPS) is increasingly being investigated as a promising potential treatment for Alzheimer's disease (AD). Although the safety and preliminary clinical efficacy of TPS short pulses have been supported by neuropsychological scores in treated AD patients, its fundamental mechanisms are uncharted.
Methods: Herein, we used a multi-modal preclinical imaging platform combining real-time volumetric optoacoustic tomography, contrast-enhanced magnetic resonance imaging, and ex vivo immunofluorescence to comprehensively analyze structural and hemodynamic effects induced by TPS.
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