Retinoic acid isomers protect hippocampal neurons from amyloid-β induced neurodegeneration
Akdeniz University, Faculty of Medicine, Department of Biochemistry and Department of Medical Biology and Genetics, Antalya- Turkey. Neurotoxicity Research
(Impact Factor: 3.54).
02/2005; 7(3):243-50. DOI: 10.1007/BF03036453
Attenuating amyloid-beta mediated neurodegeneration is of major therapeutic consideration in the potential treatment of Alzheimer disease. Previously, we found that a high dietary consumption of retinoic acid was associated with a reduced incidence of Alzheimer disease. Therefore, in this study, we investigated whether amyloid-beta mediated cell death in primary hippocampal neurons could be prevented by retinoic acid isomers. Our results suggest that retinoic acid isomers, including all-trans retinoic acid, 9-cis retinoic acid, and 13-cis retinoic acid, may play an important role in protecting neurons from amyloid-beta -induced cell death. Retinoic acid may therefore afford a novel therapeutic mechanism for the treatment and prevention of Alzheimer disease.
Available from: M.o Obulesu
- "The neuroprotective effect of ATRA observed in APP/PS1 mice is closely associated with a study demonstrating its defensive role against Ab-induced injury of primary hippocampal neuronal cultures (Sahin et al., 2005). Since ATRA substantially circumvents the reduction in ChAT induced by Ab peptides (Sahin et al., 2005), it may open a possible therapeutic avenue for AD by restoring ChAT levels (Ding et al., 2008). Intracerebral injection of acetretin, a synthetic retinoid, enhanced APPsa/APPsb ratio of 40% in cortical tissue samples of APP/PS1–21 double transgenic mice (Tippmann et al., 2009). "
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ABSTRACT: Carotenoids play a pivotal role in prevention of many degenerative diseases mediated by oxidative stress including neurodegenerative diseases like Alzheimer's Disease (AD). The involvement of retinoids in physiology, AD pathology and their therapeutic role in vitro and in vivo has been extensively studied. This review focuses on the role of carotenoids like retinoic acid (RA), all trans retinoic acid (ATRA), lycopene and β-carotene in prevention of AD symptoms primarily through inhibition of amyloid beta (Aβ) formation, deposition and fibril formation either by reducing the levels of p35 or inhibiting corresponding enzymes. The role of antioxidant micronutrients in prevention or delaying of AD symptoms has been included. This study emphasizes the dietary supplementation of carotenoids to combat AD and warrants further studies on animal models to unravel their mechanism of neuroprotection.
Neurochemistry International 06/2011; 59(5):535-41. DOI:10.1016/j.neuint.2011.04.004 · 3.09 Impact Factor
Available from: Serge Alfos
- "Some authors have reported that (i) hypo-functioning of retinoid signaling pathway is a key factor in development of AD (Goodman and Pardee, 2003), and (ii) disruption of retinoid signaling causes deposition of hamyloid in the adult brain (Corcoran et al., 2004). Finally, vitamin A or retinoid seems to impair and destabilize preformed Ah aggregates and consequently seems to protect against plaque formation, probably via its nuclear receptors (Ono et al., 2004; Sahin et al., 2005). Such effects of vitamin A are of primary importance in that attenuating Ah mediated neuro-degeneration is, today, of major consideration in a potential treatment for AD. "
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ABSTRACT: Recent data have revealed that disruption of vitamin A signaling observed in Alzheimer's disease (AD) leads to a deposition of beta-amyloid (Abeta). The aim of this study was to precise the role of vitamin A and its nuclear receptors (RAR) in the processes leading to the Abeta deposits. Thus, the effect of vitamin A depletion and subsequent administration of retinoic acid (RA, the active metabolite of vitamin A) on the expression of RARbeta, and of proteins involved in amyloidogenic pathway, e.g., amyloid precursor protein (APP), beta-secretase enzyme (BACE), and APP carboxy-terminal fragment (APP-CTF) was examined in the whole brain, hippocampus, striatum, and cerebral cortex of rats. Rats fed a vitamin A-deprived diet for 13 weeks exhibited decreased amount of RARbeta, APP695, BACE, and of APP-CTF in the whole brain and in the cerebral cortex. Administration of RA is able to restore all expression. The results suggest that fine regulation of vitamin A mediated gene expression seems fundamental for the regulation of APP processing.
Neurobiology of Disease 08/2006; 23(1):1-10. DOI:10.1016/j.nbd.2006.01.008 · 5.08 Impact Factor
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ABSTRACT: Vitamin A (retinoid) is required in the adult brain to enable cognition, learning, and memory. While brain levels of retinoid diminish over the course of normal ageing, retinoid deficit is greater in late onset Alzheimer disease (LOAD) brains than in normal-aged controls. This paper reviews recent evidence supporting these statements and further suggests that genes necessary for the synthesis, transport and function of retinoid to and within the ageing brain are appropriate targets for treatment of LOAD. These genes tend to be clustered with genes that have been proposed as candidates in LOAD, are found at chromosomal regions linked to LOAD, and suggest the possibility of an overall coordinated regulation. This phenomenon is termed Chromeron and is analogous to the operon mechanism observed in prokaryotes. Suggested treatment targets are the retinoic-acid inactivating enzymes (CYP26)s, the retinol binding and transport proteins, retinol-binding protein (RBP)4 and transthyretin (TTR), and the retinoid receptors. TTR as a LOAD target is the subject of active investigation. The retinoid receptors and the retinoid-inactivating enzymes have previously been proposed as targets. This is the first report to suggest that RBP4 is an amenable treatment target in LOAD. RBP4 is elevated in type-2 diabetes and obesity, conditions associated with increased risk for LOAD. Fenretinide, a novel synthetic retinoic acid (RA) analog lowers RBP4 in glucose intolerant obese mice. The feasibility of using fenretinide either as an adjunct to present LOAD therapies, or on its own as an early prevention strategy should be determined.
Journal of Cellular Physiology 12/2006; 209(3):598-603. DOI:10.1002/jcp.20784 · 3.84 Impact Factor
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