AI Article Synopsis
- Researchers are studying the effectiveness of 3,6'-dithioPomalidomide in reducing neuroinflammation in 5xFAD Alzheimer's mice to see if it helps combat neuronal loss and cognitive decline.
- Previous Alzheimer's treatments targeting amyloid-β or tau haven't worked well, so there's a need to find new therapeutic targets, with a focus on TNF-α as a key player in neuroinflammation.
- The study faces challenges such as getting TNF-α-lowering drugs into the brain and finding the right timing for treatment to maintain its benefits while managing neuroinflammation.
Article Abstract
Objective: Evaluating the efficacy of 3,6'-dithioPomalidomide in 5xFAD Alzheimer's disease (AD) mice to test the hypothesis that neuroinflammation is directly involved in the development of synaptic/neuronal loss and cognitive decline.
Background: Amyloid-β (Aβ) or tau-focused clinical trials have proved unsuccessful in mitigating AD-associated cognitive impairment. Identification of new drug targets is needed. Neuroinflammation is a therapeutic target in neurodegenerative disorders, and TNF-α a pivotal neuroinflammatory driver.
New Hypothesis: AD-associated chronic neuroinflammation directly drives progressive synaptic/neuronal loss and cognitive decline. Pharmacologically mitigating microglial/astrocyte activation without altering Aβ generation will define the role of neuroinflammation in AD progression.
Major Challenges: Difficulty of TNF-α-lowering compounds reaching brain, and identification of a therapeutic-time window to preserve the beneficial role of neuroinflammatory processes.
Linkage To Other Major Theories: Microglia/astroglia are heavily implicated in maintenance of synaptic plasticity/function in healthy brain and are disrupted by Aβ. Mitigation of chronic gliosis can restore synaptic homeostasis/cognitive function.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9437140 | PMC |
| http://dx.doi.org/10.1002/alz.12610 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
L-carnitine protects against oxidative damage and neuroinflammation in cerebral cortex of rats submitted to chronic chemically-induced model of hyperphenylalaninemia.
Metab Brain Dis
January 2025
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Avenida Ipiranga, 2752, Porto Alegre, CEP 90610-000, RS, Brazil.
Phenylketonuria is a genetic disorder characterized by high phenylalanine levels, the main toxic metabolite of the disease. Hyperphenylalaninemia can cause neurological impairment. In order to avoid this symptomatology, patients typically follow a phenylalanine-free diet supplemented with a synthetic formula that provides essential amino acids, including L-carnitine.
View Article and Find Full Text PDFThe endocannabinoid N-arachidonoylethanolamine (AEA) is a pro-homeostatic bioactive lipid known for its anti-inflammatory, anti-oxidative, immunomodulatory, and neuroprotective properties, which may contrast/mitigate Alzheimer's disease (AD) pathology. This study explores the therapeutic potential of targeting fatty acid amide hydrolase (FAAH), the major enzyme degrading AEA, in mouse models of amyloidosis (APP/PS1 and Tg2576). Enhancing AEA signaling by genetic deletion of FAAH delayed cognitive deficits in APP/PS1 mice and improved cognitive symptoms in 12-month-old AD-like mice.
View Article and Find Full Text PDFSatellite microglia: marker of traumatic brain injury and regulator of neuronal excitability.
J Neuroinflammation
January 2025
Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, 98104, USA.
Traumatic brain injury is a leading cause of chronic neurologic disability and a risk factor for development of neurodegenerative disease. However, little is known regarding the pathophysiology of human traumatic brain injury, especially in the window after acute injury and the later life development of progressive neurodegenerative disease. Given the proposed mechanisms of toxic protein production and neuroinflammation as possible initiators or contributors to progressive pathology, we examined phosphorylated tau accumulation, microgliosis and astrogliosis using immunostaining in the orbitofrontal cortex, a region often vulnerable across traumatic brain injury exposures, in an age and sex-matched cohort of community traumatic brain injury including both mild and severe cases in midlife.
View Article and Find Full Text PDFChronic high fat diet-induced cerebrovascular remodeling impairs recovery of blood flow after cerebral ischemia in mice.
J Cereb Blood Flow Metab
January 2025
Department of Anesthesiology, University of Virginia, Charlottesville, VA, USA.
Obesity and associated metabolic disturbances worsen brain ischemia outcome. High fat diet (HFD)-fed mice are obese and have cerebrovascular remodeling and worsened brain ischemia outcome. We determined whether HFD-induced cerebrovascular remodeling impaired reperfusion to the ischemic penumbra.
View Article and Find Full Text PDFNetwork-Based Drug Optimization toward the Treatment of Parkinson's Disease: NRF2, MAO-B, Oxidative Stress, and Chronic Neuroinflammation.
J Med Chem
January 2025
Consejo Superior de Investigaciones Científicas (IQM-CSIC), Instituto de Química Médica, 28006 Madrid, Spain.
Parkinson's disease (PD), the second most common neurodegenerative disorder, affects around 10 million people worldwide. It is a multifactorial disease marked by dopaminergic neuron loss with oxidative stress (OS) and neuroinflammation as key pathological drivers. Current treatments focus on dopamine replacement and are symptomatic, underscoring the urgent need for disease-modifying therapies.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!