Aberrant Neuronal Cell Cycle Re-Entry: The Pathological Confluence of Alzheimer's Disease and Brain Insulin Resistance, and Its Relation to Cancer

被引：25

作者：

Koseoglu, Mehmet Murat ^{[1
]}

Norambuena, Andres ^{[2
]}

Sharlow, Elizabeth R. ^{[1
]}

Lazo, John S. ^{[1
,3
,4
]}

Bloom, George S. ^{[2
,5
,6
]}

机构：

[1] Univ Virginia, Dept Pharmacol, POB 800735, Charlottesville, VA 22908 USA

[2] Univ Virginia, Dept Biol, POB 400328, Charlottesville, VA 22904 USA

[3] Univ Virginia, Dept Chem, Charlottesville, VA USA

[4] Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA USA

[5] Univ Virginia, Dept Cell Biol, Charlottesville, VA USA

[6] Univ Virginia, Dept Neurosci, Charlottesville, VA USA

来源：

JOURNAL OF ALZHEIMERS DISEASE | 2019年 / 67卷 / 01期

关键词：

Alzheimer's disease; amyloid; cell cycle re-entry; tau; TRANS-FARNESYLTHIOSALICYLIC ACID; DEPENDENT KINASE INHIBITORS; AMYLOID-BETA OLIGOMERS; SIGNALING PATHWAY; PYRAMIDAL NEURONS; S-TRANS; EXPRESSION; ACTIVATION; DEATH; METABOLISM;

D O I：

10.3233/JAD-180874

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：1 / 11

页数：11