TY - JOUR
T1 - Aberrant Neuronal Cell Cycle Re-Entry
T2 - The Pathological Confluence of Alzheimer's Disease and Brain Insulin Resistance, and Its Relation to Cancer
AU - Koseoglu, Mehmet Murat
AU - Norambuena, Andrés
AU - Sharlow, Elizabeth R.
AU - Lazo, John S.
AU - Bloom, George S.
N1 - Funding Information:
The emerging findings about intracellular signaling of AβO-mediated neuronal CCR reveals convergence points among AD, cancer and BIR. This signaling pathway commonality that connects different diseases raises the possibility that The authors greatly appreciate the generous financial support from the Owens Family Foundation (GSB, and JSL), NIH (grant RF1 AG051085 to GSB and P30 CA044579 to JSL), the Cure Alzheimer’s Fund (GSB, ERS, and JSL), the Alzheimer’s Association (grants 4079 and ZEN-16-363266 to GSB), Webb and Tate Wilson (GSB), The Virginia Chapter of the Lady’s Auxiliary of the Fraternal Order of Eagles (GSB), the University of Virginia President’s Fund for Excellence (GSB), the Department of Defense (grant BC170507 to JSL), the Fiske Drug Discovery Fund (JSL and ERS), and the Alzheimer’s and Related Diseases Research Award Fund (grant 17-5 to AN).
Funding Information:
The authors greatly appreciate the generous financial support from the Owens Family Foundation (GSB, and JSL), NIH (grant RF1 AG051085 to GSB and P30 CA044579 to JSL), the Cure Alzheimer's Fund (GSB, ERS, and JSL), the Alzheimer's Association (grants 4079 and ZEN-16-363266 to GSB), Webb and Tate Wilson (GSB), The Virginia Chapter of the Lady's Auxiliary of the Fraternal Order of Eagles (GSB), the University of Virginia President's Fund for Excellence (GSB), the Department of Defense (grant BC170507 to JSL), the Fiske Drug Discovery Fund (JSL and ERS), and the Alzheimer's and Related Diseases Research Award Fund (grant 17-5 to AN).
Publisher Copyright:
© 2019 IOS Press and the authors. All rights reserved.
PY - 2019
Y1 - 2019
N2 - Aberrant neuronal cell cycle re-entry (CCR) is a phenomenon that precedes and may mechanistically lead to a majority of the neuronal loss observed in Alzheimer's disease (AD). Recent developments concerning the regulation of aberrant neuronal CCR in AD suggest that there are potential intracellular signaling "hotspots" in AD, cancer, and brain insulin resistance, the latter of which is characteristically associated with AD. Critically, these common signaling nodes across different human diseases may represent currently untapped therapeutic opportunities for AD. Specifically, repurposing of existing US Food and Drug Administration-approved pharmacological agents, including experimental therapeutics that target the cell cycle in cancer, may be an innovative avenue for future AD-directed drug discovery and development. In this review we discuss overlapping aspects of AD, cancer, and brain insulin resistance from the perspective of neuronal CCR, and consider strategies to exploit them for prevention or therapeutic intervention of AD.
AB - Aberrant neuronal cell cycle re-entry (CCR) is a phenomenon that precedes and may mechanistically lead to a majority of the neuronal loss observed in Alzheimer's disease (AD). Recent developments concerning the regulation of aberrant neuronal CCR in AD suggest that there are potential intracellular signaling "hotspots" in AD, cancer, and brain insulin resistance, the latter of which is characteristically associated with AD. Critically, these common signaling nodes across different human diseases may represent currently untapped therapeutic opportunities for AD. Specifically, repurposing of existing US Food and Drug Administration-approved pharmacological agents, including experimental therapeutics that target the cell cycle in cancer, may be an innovative avenue for future AD-directed drug discovery and development. In this review we discuss overlapping aspects of AD, cancer, and brain insulin resistance from the perspective of neuronal CCR, and consider strategies to exploit them for prevention or therapeutic intervention of AD.
KW - Alzheimer's disease
KW - amyloid
KW - cell cycle re-entry
KW - tau
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U2 - 10.3233/JAD-180874
DO - 10.3233/JAD-180874
M3 - Review article
C2 - 30452418
AN - SCOPUS:85059854322
SN - 1387-2877
VL - 67
SP - 1
EP - 11
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 1
ER -
