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P2‐059: Intraneuronal Amylin Deposition, Peroxidative Membrane Injury and Increased IL‐1SS Synthesis in Brains of Alzheimer’s Disease Patients with Type‐2 Diabetes and Diabetic Hip Rats
Author(s) -
Despa Florin,
Verma Nirmal,
Ly Han,
Liu Miao,
Chen Jing,
Zhu Haining,
Hersh Louis
Publication year - 2016
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2016.06.1264
Subject(s) - amylin , medicine , endocrinology , amyloid (mycology) , chemistry , islet , type 2 diabetes , diabetes mellitus , inorganic chemistry
Background: Alzheimer disease (AD) is characterized by accumulation of amyloid-b plaques from the amyloid precursor protein, neurofibrillary tangles, widespread synaptic loss, inflammation, oxidative damage and neuronal death. Animal models have become an indispensable tool, both to increase the knowledge about the pathology of the disease, as well as, for the discovery of novel pharmaceutical preparations for the treatment of AD. However, there are a lot of examples of pharmaceutical preparations that have been developed for the treatment of AD and the results obtained in preclinical studies, have not been reproduced in the clinical studies. Among the causes of low clinical efficacy of these pharmaceutical preparations, it is the choosing of the suitable animal model during the preclinical phase of research. The objective of this work it’s to propose a strategy to allow us to minimize such difficulty. Methods:We suggest starting with identification of the therapeutic “goal” of the preparation inside the physiology of the AD. Another phase should be to choose the specific groups of patients to evaluate the preparation, and finally to select the appropriate experimental models, or the combination of them. This last step should take into account a logical sequential order of complexity, from in vitro to in vivo experimental models. Results: As an example of application of the proposed strategy, this work includes the selection of animal models to evaluate natural products to revert the insulin resistance and the neuroinflammation. Conclusions:This strategy contributed to increase the quality of preclinical studies.