Activation of oncogenic pathways in degenerating neurons in Alzheimer disease.
A number of recent findings have highlighted the similarities between neurogenesis during development and neurodegeneration during Alzheimer disease. In fact, neuronal populations that are known to degenerate in Alzheimer disease exhibit phenotypic changes characteristic of cells re-entering the cell division cycle. In this study, we extended these findings by investigating components of the cell cycle, known to trigger progression through G1 through activation of signal transduction cascades. Specifically, we found that proteins implicated in G1 transition, namely Cdc42/Rac, are upregulated in select neuronal populations in cases of Alzheimer disease in comparison to age-matched controls. Importantly, Cdc42/Rac shows considerable overlap with early cytoskeletal abnormalities suggesting that these changes are an extremely proximal event in the pathogenesis of the disease. Given the functional role of Cdc42/Rac in various cellular processes known to be perturbed in Alzheimer disease, namely cytoskeletal organization, oxidative balance, and oncogenic signaling, it is likely that increased neuronal Cdc42/Rac is highly significant in relation to the pathogenic process and contributes to neuronal degeneration. In fact, these findings suggest that Alzheimer disease is an oncogenic process.
Zhu
X
X
Institute of Pathology, Case Western Reserve University, Cleveland, USA.
Raina
A K
AK
Boux
H
H
Simmons
Z L
ZL
Takeda
A
A
Smith
M A
MA
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology*; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008875:Middle Aged; D009410:Nerve Degeneration / Q000235:genetics / Q000473:pathology*; D009474:Neurons / Q000737:chemistry / Q000502:physiology; D009857:Oncogenes / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D020764:cdc42 GTP-Binding Protein / Q000032:analysis / Q000502:physiology; D020744:rac GTP-Binding Proteins / Q000032:analysis / Q000502:physiology
D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins