![]() Iron is an essential element needed for vital processes such as neuronal development, myelination, synthesis and catabolism of neurotransmitters, electron transport, and iron–sulfur cluster synthesis ( Beard and Connor, 2003). The FTH1 subunit has a potent ferroxidase activity that catalyzes the oxidation of ferrous iron, whereas the FTL subunit plays a role in iron nucleation and protein stability, giving ferritin the dual functions of iron detoxification and iron reserve. Mammalian ferritins are heteropolymers composed of 24 polypeptide subunits that contain variable proportions of the light (FTL) and heavy (FTH1) polypeptide subunits ( Harrison and Arosio, 1996). This new transgenic mouse represents a relevant model of HF in which to study the pathways that lead to neurodegeneration in HF, to evaluate the role of iron mismanagement in neurodegenerative disorders, and to evaluate potential therapies for HF and related neurodegenerative diseases. Expression of the transgene in mice leads to a significant decrease in motor performance and a shorter life span, formation of ferritin inclusion bodies, misregulation of iron metabolism, accumulation of ubiquitinated proteins, and incorporation of elements of the proteasome into inclusions. Our studies show histological, immunohistochemical, and biochemical similarities between ferritin inclusion bodies found in transgenic mice and in individuals with HF. As in HF, ferritin inclusions are seen in glia and neurons throughout the CNS as well as in cells of other organ systems. ![]() Here we report that the expression in transgenic mice of a human FTL cDNA carrying a thymidine and cytidine insertion at position 498 ( FTL498–499InsTC) leads to the formation of nuclear and cytoplasmic ferritin inclusion bodies. HF is characterized by a severe movement disorder and by the presence of nuclear and cytoplasmic ferritin inclusion bodies in glia and neurons throughout the CNS and in tissues of multiple organ systems. The finding that mutations in the ferritin light polypeptide ( FTL) gene cause a neurodegenerative disease known as neuroferritinopathy or hereditary ferritinopathy (HF) provided a direct connection between abnormal brain iron storage and neurodegeneration. Continued abuse of our services will cause your IP address to be blocked indefinitely.Increased iron levels and iron-mediated oxidative stress play an important role in the pathogenesis of many neurodegenerative diseases. Please fill out the CAPTCHA below and then click the button to indicate that you agree to these terms. If you wish to be unblocked, you must agree that you will take immediate steps to rectify this issue. If you do not understand what is causing this behavior, please contact us here. If you promise to stop (by clicking the Agree button below), we'll unblock your connection for now, but we will immediately re-block it if we detect additional bad behavior. ![]() Overusing our search engine with a very large number of searches in a very short amount of time.Using a badly configured (or badly written) browser add-on for blocking content.Running a "scraper" or "downloader" program that either does not identify itself or uses fake headers to elude detection.Using a script or add-on that scans GameFAQs for box and screen images (such as an emulator front-end), while overloading our search engine.There is no official GameFAQs app, and we do not support nor have any contact with the makers of these unofficial apps. ![]() Continued use of these apps may cause your IP to be blocked indefinitely. This triggers our anti-spambot measures, which are designed to stop automated systems from flooding the site with traffic. Some unofficial phone apps appear to be using GameFAQs as a back-end, but they do not behave like a real web browser does.Using GameFAQs regularly with these browsers can cause temporary and even permanent IP blocks due to these additional requests. If you are using Maxthon or Brave as a browser, or have installed the Ghostery add-on, you should know that these programs send extra traffic to our servers for every page on the site that you browse.The most common causes of this issue are: Your IP address has been temporarily blocked due to a large number of HTTP requests.
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