Bile acids and apoptosis modulation: an emerging role in experimental Alzheimer's disease

Rita M. Ramalho, Ricardo J S Viana, Walter C. Low, Clifford J. Steer, Cecília M P Rodrigues

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

Abstract

The potential role of apoptosis in Alzheimer's disease (AD) has been an area of intense research in recent years. Ursodeoxycholic acid (UDCA) and its taurine-conjugate, tauroursodeoxycholic acid (TUDCA) are endogenous bile acids that act as potent inhibitors of apoptosis. Their therapeutic effects have been tested in many experimental pathological conditions, including neurological disorders, such as AD. TUDCA regulates precise transcriptional and post-transcriptional events that impact mitochondrial function in neurons. TUDCA not only stabilizes the mitochondrial membrane and prevents Bax translocation, inhibiting the release of cytochrome c and the activation of caspases, but also interferes with upstream factors, including cell cycle-related proteins. In addition, TUDCA is capable of inducing survival pathways. Here, we review the role of apoptosis in AD and discuss the therapeutic potential of TUDCA in treating this disease.

Original languageEnglish (US)
Pages (from-to)54-62
Number of pages9
JournalTrends in Molecular Medicine
Volume14
Issue number2
DOIs
StatePublished - Feb 2008

Bibliographical note

Funding Information:
Supported in part by grants PPCDT/SAU-MMO/57936/2004 and PTDC/SAU-FCF/67912/2006 from Fundação para a Ciência e Tecnologia (FCT), Lisbon, Portugal. R.M.R and R.J.S.V. were recipients of Ph.D. fellowships (SFRH/BD/12641/2003 and SFRH/BD/30467/2006, respectively) from FCT. The authors thank all members of the laboratory for critical reading of the manuscript.

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