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P1‐302: MMP‐9 attenuates amyloid plaque pathogenesis in APP/PS1 mice
Author(s) -
Lee Jin- Moo,
Wang Yan,
Hu Xiaoyan,
Kraft Andrew,
Xiao Qingli,
Yan Ping
Publication year - 2010
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.2010.05.855
Subject(s) - astrocyte , senile plaques , pathology , mmp9 , immunohistochemistry , immunostaining , pathogenesis , amyloid (mycology) , amyloid precursor protein , presenilin , biology , chemistry , microbiology and biotechnology , alzheimer's disease , medicine , endocrinology , gene , downregulation and upregulation , biochemistry , central nervous system , disease
Background: Homosapiens have a slow life, even compared to the most related primates. Beside the well known particular morphological and physiological traits, this species experiences some particularities of the agingrelated pathology. Humans suffer from Alzheimer’s disease, autoimmune diseases, and have a greater risk of developing type II diabetes and cancer than chimpanzees in lab. The huge human brain has also a particular pathology, beside Alzheimer’s disease, including psychiatric disorders, autism etc. A hypothesis able to explain the mechanisms of human evolution must explain the appearance and mechanism of the specific human brain diseases. Methods: Three general classes of genetic differences have been proposed as factors separating humans from the great apes: chromosomal differences, small sequence differences that change gene expression, and biochemical changes resulting from gene inactivation. The molecular biology data support the idea that epigenetic changes could result in all the genetic differences mentioned above. As a result, some important biochemical pathways, with crucial role in organism development, could suffer changes in regulation and activity. We tried to identify such pathways. Results: One such signaling pathway (insulin/IGF1) involved in metamorphosis in some species, cell proliferation and differentiation, is also altered in psychiatric disorders, autism, Alzheimer’s, diabetes and other diseases. Changes in the activity of this pathway resulting in altered cell proliferation/ differentiation patterns could determine the development of some human unique traits, such as the huge brain. On the other side, the incidence of Alzheimer’s disease is 2 fold higher in the type II diabetes patients. Also, factors that determine insulin resistance (streptozotocine) determine activity changes of a key enzyme involved in the insulin/IGF1 pathway similar to those in Alzheimer’s disease. In such conditions, Alzheimer’s disease could be seen as a brain’s diabetes. Some data suggest that the cellular and tissue markers of this malady, such as the tau protein alteration and the amyloid aggregations could be consequences of the alteration of the brain glucose and lipid metabolism. The preamyloid protein enhances the signaling of the mentioned pathway. Conclusions: This hypothesis could provide a new theoretical approach as well as new therapeutic strategies for common human diseases.