TY - JOUR
T1 - Functional analyses of major cancer-related signaling pathways in Alzheimer's disease etiology
AU - Guo, Jianping
AU - Cheng, Ji
AU - North, Brian J.
AU - Wei, Wenyi
N1 - Funding Information:
The authors sincerely apologize to all those colleagues whose important work was not cited in this paper owing to space limitations. They thank the members of Wei laboratory for critical reading and discussion of the manuscript. B.J.N. was supported in part by NIH K01 grant AG052627. W.W. is a Leukemia & Lymphoma Society (LLS) research scholar. This work was supported in part by Scientific Research Training Program for young talents of Union Hospital, Tongji Medical College (201701) to J.C. and by US National Institutes of Health (NIH) grants to W.W. (GM094777 and CA177910).
Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2017/12
Y1 - 2017/12
N2 - Alzheimer's disease (AD) is an aging-related neurodegenerative disease and accounts for majority of human dementia. The hyper-phosphorylated tau-mediated intracellular neurofibrillary tangle and amyloid β-mediated extracellular senile plaque are characterized as major pathological lesions of AD. Different from the dysregulated growth control and ample genetic mutations associated with human cancers, AD displays damage and death of brain neurons in the absence of genomic alterations. Although various biological processes predominately governing tumorigenesis such as inflammation, metabolic alteration, oxidative stress and insulin resistance have been associated with AD genesis, the mechanistic connection of these biological processes and signaling pathways including mTOR, MAPK, SIRT, HIF, and the FOXO pathway controlling aging and the pathological lesions of AD are not well recapitulated. Hence, we performed a thorough review by summarizing the physiological roles of these key cancer-related signaling pathways in AD pathogenesis, comprising of the crosstalk of these pathways with neurofibrillary tangle and senile plaque formation to impact AD phenotypes. Importantly, the pharmaceutical investigations of anti-aging and AD relevant medications have also been highlighted. In summary, in this review, we discuss the potential role that cancer-related signaling pathways may play in governing the pathogenesis of AD, as well as their potential as future targeted strategies to delay or prevent aging-related diseases and combating AD.
AB - Alzheimer's disease (AD) is an aging-related neurodegenerative disease and accounts for majority of human dementia. The hyper-phosphorylated tau-mediated intracellular neurofibrillary tangle and amyloid β-mediated extracellular senile plaque are characterized as major pathological lesions of AD. Different from the dysregulated growth control and ample genetic mutations associated with human cancers, AD displays damage and death of brain neurons in the absence of genomic alterations. Although various biological processes predominately governing tumorigenesis such as inflammation, metabolic alteration, oxidative stress and insulin resistance have been associated with AD genesis, the mechanistic connection of these biological processes and signaling pathways including mTOR, MAPK, SIRT, HIF, and the FOXO pathway controlling aging and the pathological lesions of AD are not well recapitulated. Hence, we performed a thorough review by summarizing the physiological roles of these key cancer-related signaling pathways in AD pathogenesis, comprising of the crosstalk of these pathways with neurofibrillary tangle and senile plaque formation to impact AD phenotypes. Importantly, the pharmaceutical investigations of anti-aging and AD relevant medications have also been highlighted. In summary, in this review, we discuss the potential role that cancer-related signaling pathways may play in governing the pathogenesis of AD, as well as their potential as future targeted strategies to delay or prevent aging-related diseases and combating AD.
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U2 - 10.1016/j.bbcan.2017.07.001
DO - 10.1016/j.bbcan.2017.07.001
M3 - Review article
C2 - 28694093
AN - SCOPUS:85025671165
VL - 1868
SP - 341
EP - 358
JO - Biochimica et Biophysica Acta - Reviews on Cancer
JF - Biochimica et Biophysica Acta - Reviews on Cancer
SN - 0304-419X
IS - 2
ER -