summary: A new study reveals how certain anti-inflammatory drugs may prove to be effective treatments for Alzheimer’s disease (AD).
The research team focused on a protein known as p38. The researchers found that stopping the production of this protein in brain immune cells reduced the concentration of these cells around amyloid plaques, a key component of AD pathology, suggesting an interaction with AD elements. It suggests that the action may change.
This study suggests that long-term suppression of p38 may not cause noticeable side effects, and early suppression may alter the course of Alzheimer’s disease.
Important facts:
- In this study, we investigated the p38 protein, a potential drug target for Alzheimer’s disease therapy.
- Researchers stopped the production of p38 in brain immune cells and observed a decrease in its interaction with amyloid plaques, a key factor in AD pathogenesis.
- This study suggests that long-term suppression of p38 may not cause noticeable side effects, and early suppression may influence AD progression.
sauce: University of Kentucky
A recent study from the lab of Dr. Linda Van Erdik, director of the Sanders Brown Center for Aging at the University of Kentucky, found that Proswan.
This research centers around the idea that different anti-inflammatory drugs could be effective treatments for Alzheimer’s disease (AD).
This study focused on a protein known as p38. Many laboratories have investigated this protein as a potential target for drug development to treat Alzheimer’s disease and other conditions associated with neuroinflammatory dysfunction.
Van Erdik and her team used genetic engineering to turn off the production of p38 in microglia, a major immune cell type in the brain. They tested this effect in an early-stage mouse model of AD to determine whether it altered the trajectory of amyloid plaque formation, a key component of AD pathogenesis.
Although the plaques themselves were unaffected, the amount of microglia adjacent to these plaques was reduced, suggesting that suppression of microglial p38 may influence its interaction with AD pathogenesis. doing.
Some classes of anti-inflammatory drugs include p38 inhibitors, which are currently in clinical development and have shown promising results in recent human clinical trials.
However, it is still unclear when these p38 inhibitors should be administered during disease progression and whether long-term suppression of p38 is harmful.
Research results reported by the Van Eldik lab show that early inhibition of p38 may be able to alter the interaction between brain immune cells and Alzheimer’s disease, and that long-term suppression of p38 can lead to significant side effects. suggests not to cause
Funding: Research reported in this publication was supported by the National Institute on Aging, National Institutes of Health with award numbers F32AG058456, T32AG057461, and RF1AG06485. The content is the sole responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
About this neuropharmacology research news
author: Mark Witt
sauce: University of Kentucky
contact: Mark Witt – University of Kentucky
image: Image credited to Neuroscience News
Original research: open access.
“Early chronic suppression of microglial p38α in an Alzheimer’s disease model does not significantly alter amyloid-associated neuropathologyby Linda Van Erdik et al. pro swan
overview
Early chronic suppression of microglial p38α in an Alzheimer’s disease model does not significantly alter amyloid-associated neuropathology
The p38 alpha mitogen-activated protein kinase (p38α) is involved in both innate and adaptive immune responses and is a target for drug development associated with Alzheimer’s disease (AD) and other conditions involving neuroinflammatory dysfunction. is under study as
Preclinical data indicate that p38α inhibition can prevent neuropathology associated with Alzheimer’s disease, but the underlying mechanisms have not been fully elucidated. Inhibitors of p38α may provide benefits through modulation of microglia-associated neuroinflammatory responses that contribute to AD pathogenesis.
In the present study, we test this hypothesis by knocking out microglial p38α and assessing early-stage pathological changes. Conditional knockout of microglial p38α was achieved in 5-month-old C57BL/6J wild-type and amyloidogenic AD model (APPswe/PS1dE9) mice using the tamoxifen-inducible Cre/loxP system under control . Cx3cr1 promoter.
Animals underwent open-field behavioral assessment at 7.5 months of age, followed by radial arm water maze testing and cortical and hippocampal tissue sampling at 11 months.
Additional endpoint measurements include quantification of proinflammatory cytokines, assessment of amyloid load and plaque deposition, and characterization of microglia-plaque dynamics. Loss of microglial p38α did not alter behavioral outcomes, levels of proinflammatory cytokines, or overall amyloid plaque load.
However, this manipulation significantly increased hippocampal soluble Aβ42 levels and reduced the colocalization of Iba1 and 6E10 in a subset of microglia in close proximity to plaques.
The data presented here suggest that rather than reducing inflammation, itself, the net effect of microglial p38α inhibition in early AD-type amyloid pathology is subtle alterations in microglia–plaque interactions. Encouraging from a therapeutic perspective, these data suggest that even a large reduction in microglial p38α in this setting has no detrimental effects.
Moreover, these results support future studies of the relationship between microglial p38α signaling at different stages of disease and the phagocytic process in this specific cell type.
