[
J Dev Biol,
2020]
Apical extracellular matrices (aECMs) coat exposed surfaces of epithelia to shape developing tissues and protect them from environmental insults. Despite their widespread importance for human health, aECMs are poorly understood compared to basal and stromal ECMs. The nematode <i>Caenorhabditis elegans</i> contains a variety of distinct aECMs, some of which share many of the same types of components (lipids, lipoproteins, collagens, zona pellucida domain proteins, chondroitin glycosaminoglycans and proteoglycans) with mammalian aECMs. These aECMs include the eggshell, a glycocalyx-like pre-cuticle, both collagenous and chitin-based cuticles, and other understudied aECMs of internal epithelia. <i>C. elegans</i> allows rapid genetic manipulations and live imaging of fluorescently-tagged aECM components, and is therefore providing new insights into aECM structure, trafficking, assembly, and functions in tissue shaping.
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Curr Alzheimer Res,
2009]
In different clinical studies, an association of type 2 diabetes and Alzheimer's disease (AD) has been described. However, the underlying mechanisms are still unclear. One explanation could be that vascular complications of diabetes result in neurodegeneration. Alternatively, the mechanism might be directly related to insulin and insulin-like growth factor(IGF)-1 signaling, leading to the proposal that AD is a "brain-type diabetes". Furthermore, postmortem analyses of brains from patients with AD revealed a markedly downregulated expression of insulin receptor (IR), IGF-1 receptor (IGF-1R), insulin receptor substrate (IRS)-1 and IRS-2, and these changes progress with severity of neurodegeneration. These findings raise the question, whether this phenomenon is cause or consequence of neurodegeneration. Recently, Cohen and coworkers have show that knocking down DAF-2 in C. elegans, the homolog of the mammalian IR/IGF-1R, reduces beta-amyloid(Abeta)(1-42) toxicity. Cell based experiments suggest a specific role for the IGF 1/IRS-2 signaling pathway in regulating alpha-/beta-secretase activity. Moreover circulating IGF-1 might influence Abeta clearance from the brain by promoting Abeta transport over the blood brain barrier. Interestingly, brain specific deletion of IRS-2 increases life span, suggesting that long term neuronal IGF-1R signaling might be harmful. Taken together, the data from humans and different model organisms indicate a role of IR/IGF-1R signaling in Abeta metabolism, and clearance as well as longevity. Since more studies are needed to elucidate the impact of insulin and/or IGF-1 treatment in AD, the time to propose these hormones as a potential treatment option for AD has not come yet.