Publications by authors named "Joia Capocchi"
Article Synopsis
- Alzheimer's disease (AD) and related dementias (ADRDs) are complex neurodegenerative diseases that pose challenges for therapy development.
- Research from the 2024 Society for Neuroscience meeting points to the gut microbiome's influence on AD development through the microbiota-gut-brain axis.
- These findings suggest that targeting the gut microbiota could open new avenues for treating AD and ADRD.
Article Synopsis
- - Microglia are the central nervous system's immune cells, playing essential roles in brain development and maintaining neuron activity, but their involvement at the blood-brain barrier (BBB) in healthy brains is less understood.
- - A study using the CSF1R inhibitor PLX5622 to deplete microglia showed that they are not crucial for maintaining the structure or function of the healthy BBB, despite their close contact with endothelial cells.
- - However, treatment with PLX5622 was found to affect cholesterol metabolism in brain endothelial cells independently of microglial presence, indicating that the drug has unintended effects on brain blood vessels.
Article Synopsis
- The urgent global challenge of Alzheimer's Disease (AD) highlights the need for innovative treatments, particularly as current options remain limited in effectiveness.
- Research is focusing on immunotherapies, like the FDA-approved lecanemab, which shows promise in reducing harmful brain aggregates, though benefits so far have been modest.
- A new universal vaccine platform, MultiTEP, has been developed, leading to the initiation of clinical trials for a DNA vaccine (AV-1959D) and a novel mRNA vaccine (AV-1959LR), which are showing promising initial immunogenicity results in animal studies.
Microglia replacement strategies are increasingly being considered for the treatment of primary microgliopathies like adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). However, available mouse models fail to recapitulate the diverse neuropathologies and reduced microglia numbers observed in patients. In this study, we generated a xenotolerant mouse model lacking the fms-intronic regulatory element (FIRE) enhancer within Csf1r, which develops nearly all the hallmark pathologies associated with ALSP.
View Article and Find Full Text PDFHematopoietic stem cell transplantation (HSCT) can replace endogenous microglia with circulation-derived macrophages but has high mortality. To mitigate the risks of HSCT and expand the potential for microglia replacement, we engineered an inhibitor-resistant CSF1R that enables robust microglia replacement. A glycine to alanine substitution at position 795 of human CSF1R (G795A) confers resistance to multiple CSF1R inhibitors, including PLX3397 and PLX5622.
View Article and Find Full Text PDFRecent evidence suggests that, similar to larger organisms, dispersal is a key driver of microbiome assembly; however, our understanding of the rates and taxonomic composition of microbial dispersal in natural environments is limited. Here, we characterized the rate and composition of bacteria dispersing into surface soil via three dispersal routes (from the air above the vegetation, from nearby vegetation and leaf litter near the soil surface, and from the bulk soil and litter below the top layer). We then quantified the impact of those routes on microbial community composition and functioning in the topmost litter layer.
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