Mitotic and gender parallels in Alzheimer disease: therapeutic opportunities.
In this review, we discuss the role of cell cycle dysfunction in the pathogenesis of Alzheimer disease and propose that such mitotic catastrophe, as one of the earliest events in neuronal degeneration, may, in fact, be sufficient to initiate the neurodegenerative cascade. The question as to what molecule initiates cell cycle dysfunction is now beginning to become understood and, in this regard, the gender-predication, age-related penetrance and regional susceptibility of specific neuronal populations led us to consider luteinizing hormone as a key mediator of the abnormal mitotic process. As such, agents targeted toward luteinizing hormone or downstream sequelae may be of great therapeutic value in the treatment of Alzheimer disease.
Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, Ohio 44106, USA.
X
X
Zhu
K M
KM
Webber
G
G
Casadesus
A K
AK
Raina
H G
HG
Lee
M
M
Marlatt
A
A
Hartzler
C S
CS
Atwood
G
G
Perry
M A
MA
Smith
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D000818:Animals; D005544:Forecasting; D006801:Humans; D008938:Mitosis / Q000187:drug effects / Q000502:physiology*; D008954:Models, Biological; D009410:Nerve Degeneration / Q000209:etiology* / Q000473:pathology; D012727:Sex Characteristics; D013678:Technology, Pharmaceutical / Q000639:trends