The second limitation that can be raised is that tissues deteriorate as a result of long-term culture.Previous studies have identified molecules that interact with PrP, some of which have been found to bind specifically to the N-terminus of PrP. These include the low-density lipoprotein receptor-related protein 1, which modulates the endocytosis of PrP. Disruption of this region prevents this endocytosis of PrP, and influences its half-life and rate of trafficking to the plasma membrane. These residues are also a binding site for GAGs, which can mediate binding between PrP and the 37 kDa/67 kDa laminin receptor. Additionally, the polybasic region is capable of interacting with the plasma membrane as a protein transduction domain or an antimicrobial peptide, although several studies indicate that its ability to insert into the membrane also requires the presence of the octapeptide repeat region. In PrP that is targeted to the cytoplasm due to abnormal folding or processing, these residues can function as a nuclear localization signal and interact with tubulin, although these interactions may not be physiologically relevant in the presence of normally processed PrP, which is localized primarily to the outer leaflet of the plasma membrane.

Whether these or other, undefined interactions are relevant to the neuroprotective function of PrP remains unresolved. Of note, a recent report identifies residues 23–27 of PrP as one of the two sites that bind oligomers of the Alzheimer’s Ab peptide, suggesting a role for this region in mediating the synaptotoxic effects of these oligomers. Given the role of the N-terminal polybasic domain in determining the neuroprotective properties of PrP, as well as its binding to other toxic oligomers, this region may prove to be an important therapeutic target in prion as well as other neurodegenerative disorders. Moderate to severe traumatic brain injury can accelerate cognitive decline and increases the risk of dementia of the Alzheimer’s type.

As levodopa solubility is pH-sensitive, alterations in gastric acidity may affect levodopa absorption. With eradication, there is normalization of gastric acid secretion, leading to better levodopa absorption and potentially improved clinical response In support, studies have demonstrated that H. pylori eradication augments the plasma levodopa concentration by up to 51% in PD patients. Expression of F4ac fimbria by ETEC on the host cell surface and also enhance ETEC adherence to the intestinal epithelium prior to fimbrial expression through alteration of the host cell membrane potential, thereby initiating colonization in the proximal small intestine.