Caffeic acid phenethyl ester prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurodegeneration

Khan

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

2013

X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder caused by mutations in the ABCD1 gene. Accumulation of very long chain fatty acids (VLCFA) that have been attributed to reduced peroxisomal VLCFA β-oxidation activity are the hallmark of the disease. Overexpression of ABCD2 gene, the closest homolog of ABCD1, has been shown to compensate for ABCD1, thus correcting the VLCFA derrangement. The accumulation of VLCFA leads to a neuroinflammatory disease process associated with demyelination of the cerebral white matter. The present study underlines the importance of caffeic acid phenethyl ester (CAPE) in inducing the expression of ABCD2 (ALDRP), and normalizing the peroxisomal β-oxidation as well as the levels of saturated and monounsaturated VLCFAs in cultured human skin fibroblasts of X-ALD patients. The expression of ELOVL1, the single elongase catalyzing the synthesis of both saturated VLCFA (C26:0) and mono-unsaturated VLCFA (C26:1), was also reduced by CAPE treatment. Importantly, CAPE upregulated Abcd2 expression and peroxisomal β-oxidation and lowered the VLCFA levels in Abcd1-deficient U87 astrocytes and B12 oligodendrocytes. In addition, using Abcd1/Abcd2-silenced mouse primary astrocytes we examined the effects of CAPE in VLCFA-induced inflammatory response. CAPE treatment decreased the inflammatory response as the expression of inducible nitric oxide synthase, inflammatory cytokine, and activation of NF-κB in Abcd1/Abcd2-silenced mouse primary astrocytes was reduced. The observations indicate that CAPE corrects both the metabolic disease of VLCFA as well as secondary inflammatory disease; therefore, it may be a potential drug candidate to be tested for X-ALD therapy in humans.

Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Caffeic acid phenethyl ester induces adrenoleukodystrophy (Abcd2) gene in human X-ALD fibroblasts and inhibits the proinflammatory response in Abcd1/2 silenced mouse primary astrocytes

Khan

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

2013

BioMed Research International

“…CAPE can obstruct apoptosis in cerebellar granule cells [72], reduce ischemia/reperfusion-provoked cerebral injury [73, 74] and spinal cord ischemia/reperfusion injury [75], and avert different toxin-provoked neurotoxicity [69, 76–79]. Moreover, CAPE efficiently suppresses NF κ B activation [55], lipid peroxidation activity [38], lipoxygenase activities [80], protein tyrosine kinase activity [81], and ornithine decarboxylase activity [82].…”

Section: Activities Of Capementioning

confidence: 99%

Caffeic Acid Phenethyl Ester and Therapeutic Potentials

Murtaza

Karim

Akram

et al. 2014

173

123

Caffeic acid phenethyl ester (CAPE) is a bioactive compound of propolis extract. The literature search elaborates that CAPE possesses antimicrobial, antioxidant, anti-inflammatory, and cytotoxic properties. The principal objective of this review article is to sum up and critically assess the existing data about therapeutic effects of CAPE in different disorders. The findings elaborate that CAPE is a versatile therapeutically active polyphenol and an effective adjuvant of chemotherapy for enhancing therapeutic efficacy and diminishing chemotherapy-induced toxicities.

“…The antioxidant compound from propolis, CAPE, has been shown to exert protective effect in different models of neurotoxicity induced (i) in vitro by glutamate (Wei et al, 2008), 6-hydroxydopamine (Noelker et al, 2005) and MPP + (1-methyl-4-phenylpyridinium), or even (ii) in vivo by MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) (Fontanilla et al, 2011). The neuroprotective effect of CAPE has been mainly attributed to its immunemodulatory, anti-inflammatory and antioxidant properties (Kasai et al, 2011;Araujo et al, 2012;Natarajan et al, 1996;Noelker et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Caffeic acid phenethyl ester (CAPE) protects PC12 cells from MPP+ toxicity by inducing the expression of neuron-typical proteins

et al. 2014

Neurite loss is an early event in neurodegenerative diseases; therefore, the regeneration of the network of neurites constitutes an interesting strategy of treatment for such disorders. Neurotrophic factors play a critical role in neuronal regeneration, but their clinical use is limited by their inability to cross the blood brain barrier. Oxidative and inflammatory events are implicated in neurodegeneration and antioxidant compounds have been suggested as potential neuroprotectors. The protective potential of CAPE (caffeic acid phenethyl ester) has been shown in different models of neurotoxicity (in vitro and in vivo) and it has been associated with immune-modulatory, antioxidant and anti-inflammatory properties; however, other mechanisms might be involved. The present study demonstrates that CAPE protects PC12 cells from the cellular death induced by the dopaminergic neurotoxin MPP(+) by increasing the network of neurites. Results showed that CAPE induced the formation, elongation and ramification of neurites in PC12 cells non-stimulated with NGF (nerve growth factor) and inhibited the shortage of neurites induced by the dopaminergic neurotoxin. These effects were associated with increased expression of neuron-typical proteins responsible for axonal growth (GAP-43) and synaptogenesis (synaptophysin and synapsin I). It is noteworthy that, unlike neurotrophins, CAPE would be able to cross the blood brain barrier and exert its neurotrophic effects in the brain. This study corroborates the therapeutic potential of CAPE in neurodegenerative diseases while proposes the involvement of neuroplasticity in the mechanism of neuroprotection.