Microglia are essential for maintaining homeostasis and responding to pathological events in the central nervous system (CNS). Their dynamic and multidimensional states in different environments are pivotal factors in various CNS disorders. However, therapeutic modulation of microglial states is challenging due to the intricate balance these cells maintain in the CNS environment and the blood-brain barrier's restriction of drug delivery. Nanomedicine presents a promising avenue for addressing these challenges, offering a method for the targeted and efficient modulation of microglial states. This review covers the challenges faced in microglial therapeutic modulation and potential use of nanoparticle-based drug delivery systems. We provide an in-depth examination of nanoparticle applications for modulating microglial states in a range of CNS disorders, encompassing neurodegenerative and autoimmune diseases, infections, traumatic injuries, stroke, tumors, chronic pain, and psychiatric conditions. This review highlights the recent advancements and future prospects in nanomedicine for microglial modulation, paving the way for future research and clinical applications of therapeutic interventions in CNS disorders.
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http://dx.doi.org/10.1016/j.biopha.2024.117011 | DOI Listing |
Alzheimers Dement
December 2024
Indiana University School of Medicine, Indianapolis, IN, USA.
Background: TREM2 signaling has been implicated in Alzheimer's Disease (AD). TREM2 regulates microglial states and functions such as phagocytosis. The most prominent TREM signaling adapter is DAP12, encoded by TYROBP.
View Article and Find Full Text PDFGlia
January 2025
Department of Biology, College of Arts and Sciences, University of Virginia, Charlottesville, Virginia, USA.
Microglia play a critical role in maintaining central nervous system (CNS) homeostasis and display remarkable plasticity in their response to inflammatory stimuli. However, the specific signaling profiles that microglia adopt during such challenges remain incompletely understood. Traditional transcriptomic approaches provide valuable insights, but fail to capture dynamic post-translational changes.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Faculty of Nursing, Tokai University School of Medicine, Isehara 259-1193, Japan.
Retrotransposon Gag-like 4 (), a gene acquired from a retrovirus, is a causative gene in autism spectrum disorder. Its knockout mice exhibit increased impulsivity, impaired short-term spatial memory, failure to adapt to novel environments, and delayed noradrenaline (NA) recovery in the frontal cortex. However, due to its very low expression in the brain, it remains unknown which brain cells express RTL4 and its dynamics in relation to NA.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Translational Neuroscience, Barrow Neurological Institute, St Joseph's Hospital and Medical Center (SJHMC), Phoenix, AZ 85013, USA.
Traumatic optic neuropathy (TON) has been regarded a vision-threatening condition caused by either ocular or blunt/penetrating head trauma, which is characterized by direct or indirect TON. Injury happens during sports, vehicle accidents and mainly in military war and combat exposure. Earlier, we have demonstrated that remote ischemic post-conditioning (RIC) therapy is protective in TON, and here we report that AMPKα1 activation is crucial.
View Article and Find Full Text PDFFront Neurosci
December 2024
The Neuro's Early Drug Discovery Unit (EDDU), McGill University, Montreal, QC, Canada.
This study aimed to evaluate different combinations of three dietary supplements for potential additive or synergistic effects in an Parkinson's Disease model. The complex and diverse processes leading to neurodegeneration in each patient with a neurodegenerative disorder cannot be effectively addressed by a single medication. Instead, various combinations of potentially neuroprotective agents targeting different disease mechanisms simultaneously may show improved additive or synergistic efficacy in slowing the disease progression and allowing the agents to be utilized at lower doses to minimize side effects.
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