科研之友
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摘要
Despite decades of research, there is no cure for Alzheimer disease (AD), and current pharmacological treatments only partially mask the symptoms while the disease progresses within the brain. AD is associated with impaired clearance of -amyloid (A) from the brain, a process facilitated by apolipoprotein E (ApoE), whose expression is transcriptionally regulated by the ligand-activated nuclear receptors peroxisome proliferator-activated receptor- (PPAR) and liver X receptor (LXR), in conjunction with retinoid X receptor (RXR). A very interesting study performed by G.E. Landreth%26apos;s group in three murine models of AD has shown that the RXR agonist bexarotene (Targretin), Food and Drug Administration (FDA) approved and used since 1999 for the treatment of cutaneous T cell lymphoma, promotes a fast ApoE-dependent clearance of soluble A peptides from the brain, reduces A plaques, and stimulates the reversal of cognitive, social, and olfactory deficits. Four independent studies tried to replicate these observations; the clearance of soluble A peptides and the reversal of cognitive deficits were replicated in two studies, but all of the studies failed to replicate the reduction of A plaques. In a second report, G.E. Landreth%26apos;s group formulates some hypotheses to explain these discrepancies. Although observations in mouse models of AD might not necessarily extrapolate to humans, bexarotene is a very interesting potential drug against AD; phase I and II clinical trials are under way.
- 出版日期2013-12-1
