The extracellular matrix (ECM) is a biological substrate composed of collagens, proteoglycans and glycoproteins that ensures proper cell migration and adhesion and keeps the cell architecture intact. The regulation of the ECM composition is a vital process strictly controlled by, among others, proteases, growth factors and adhesion receptors. As it appears, ECM remodeling is also essential for proper neuronal and glial development and the establishment of adequate synaptic signaling. Hence, disturbances in ECM functioning are often present in neurodegenerative diseases like Alzheimer’s disease. Moreover, mutations in ECM molecules are found in some forms of epilepsy and malfunctioning of ECM-related genes and pathways can be seen in, for example, cancer or ischemic injury. Low density lipoprotein receptor-related protein 1 (Lrp1) is a member of the low density lipoprotein receptor family. Lrp1 is involved not only in ligand uptake, receptor mediated endocytosis and lipoprotein transport—functions shared by low density lipoprotein receptor family members—but also regulates cell surface protease activity, controls cellular entry and binding of toxins and viruses, protects against atherosclerosis and acts on many cell signaling pathways. Given the plethora of functions, it is not surprising that Lrp1 also impacts the ECM and is involved in its remodeling. This review focuses on the role of Lrp1 and some of its major ligands on ECM function. Specifically, interactions with two Lrp1 ligands, integrins and tissue plasminogen activator are described in more detail.
The Alzheimer disease-associated multifunctional low-density lipoprotein receptorrelated protein-1 is expressed in the brain. Recent studies uncovered a role of this receptor for the appropriate functioning of neural stem cells, oligodendrocytes, and neurons. The constitutive knockout (KO) of the receptor is embryonically lethal. To unravel the receptors' role in the developing brain we generated a mouse mutant by specifically targeting radial glia stem cells of the dorsal telencephalon. The lowdensity lipoprotein receptor-related protein-1 lineage-restricted KO female and male mice, in contrast to available models, developed a severe neurological phenotype with generalized seizures during early postnatal development. The mechanism leading to a buildup of hyperexcitability and emergence of seizures was traced to a failure in adequate astrocyte development and deteriorated postsynaptic density integrity. The detected impairments in the astrocytic lineage: precocious maturation, reactive gliosis, abolished tissue plasminogen activator uptake, and loss of functionality emphasize the importance of this glial cell type for synaptic signaling in the developing brain. Together, the obtained results highlight the relevance of astrocytic lowdensity lipoprotein receptor-related protein-1 for glutamatergic signaling in the
Most studies on the effects of water quality on amphibians concern experimental conditions. The main aim of our study was to determine whether the quality of water bodies in urban environment may be a factor leading to local extinction of some amphibian species. We investigated the current amphibian richness in Kraków water bodies and the water quality of these water bodies. We compared our results with available historical data on amphibian richness in Kraków and we determined the number of amphibian species local extinction for each water body. Then, we compared water bodies with low amphibian extinction rates to water bodies with high amphibian extinction rates in respect to ten water quality chemical indicators. We found that the values of most chemical indicators were higher in water bodies with high amphibian extinction rates. The values of magnesium and chloride ion concentration, as well as conductivity appeared to differ the most between these two types of water bodies which is connected mainly with spring runoff into the water bodies. The results of this study demonstrate that water pollution may lead to local extinction of amphibian species.
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