In addition, PA1637 as well as other bis-quinoline derivatives is able to inhibit the aggregation of amyloid peptides. Moreover, this non-transgenic mouse model presents the additional advantages of being fast, easy to implement, reliable and reproducible in independent experiments as indicated by low standard errors. During the conditioning session, irrespective to the applied treatment, mice showed similar initial levels of freezing and behaved similarly in response to the unconditional stimulus, displaying a large increase of freezing in response to the electric shock. Consequently, the different treatments did not induce variations of stress or activity during the training session. Furthermore, reactivity and short term memory of mice conditioned using the single trial training procedure were not impaired by the pharmacological treatments since mice of the different groups exhibited similar levels of freezing during the 30 sec period following the administration of the electric shock. On the other hand, during the contextual-fear memory assay that occurred 24 h after conditioning, Ab1–42 mice showed impaired freezing, revealing a meaningful episodic memory deficit. The validity of the presently described Ab1–42 icv model is also established by the positive effect of three different molecules, two chelators, PA1637 and clioquinol, and memantine, a NMDA antagonist to inhibit the loss of episodic memory. Such non-transgenic mice model should not be considered as a complete AD animal model, but as a useful tool for rapid screening of drug-candidates. Additional studies will be Semaxanib 204005-46-9 performed in the future to evaluate the limits of this amyloid model. Geographic atrophy is characterized by confluent areas of cell death in photoreceptors and retinal pigment epithelium and is responsible for 10% of the cases of legal blindness resulting from age-related macular degeneration. Both cataract and GA are strongly age related. The association between cataract surgery and the development of GA was controversial in previous studies. In the Beaver Dam Eye Study, a positive cross-sectional association was found between cataract surgery and GA. The association was consistent with findings in the Los Angeles Latino Eye Study, but not with findings in the Blue Mountains Eye Study or the Age-related Eye Disease Study. However, the positive association between cataracts and GA was consistent in the Beaver Dam Eye Study and LALES. The pathogenesis of the association between cataract surgery and GA is less clear. The previous hypothesis is that cataract removal results in increased risk because the cataract, a barrier to ultraviolet radiation, has been removed. Based on this hypothesis, in theory, the prevalence of GA should be decreased in patients with cataract. However, the truth is that the prevalence of GA is higher in patients with cataract than the control. Therefore, this hypothesis is not sufficient to explain the clinical phenomenon. One common change involving cataracts and cataract surgery has been neglected: the change of a-crystallins, which are the major protein of lens. The a-crystallins are small heat shock proteins which play central roles in maintaining lens transparency and refractive properties. The discovery in 1992 that these proteins possess chaperone-like activity has led most researchers to focus on the ability of a-crystallins to prevent protein aggregation in vitro. While the ability of a-crystallins to efficiently trap aggregation-prone denatured proteins in vitro is thought to delay the development of age-related cataracts in vivo, a-crystallins have additional functions which may also contribute to cataract pathology.