2015
DOI: 10.7603/s40681-015-0004-y
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Irisflorentin improves α-synuclein accumulation and attenuates 6-OHDA-induced dopaminergic neuron degeneration, implication for Parkinson’s disease therapy

Abstract: Parkinson’s disease (PD) is a degenerative disorder of the central nervous system that is characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta as well as motor impairment. Aggregation of α-synuclein in neuronal cells plays a key role in this disease. At present, therapeutics for PD provides moderate symptomatic benefits, but it is not able to delay the development of the disease. Current efforts toward the treatment of PD are to identify new drugs that slow or arrest … Show more

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Cited by 27 publications
(14 citation statements)
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“…Proper RPN-3 levels are critical for proteasome function as either overexpression or deletion of rpn-3 disrupted the function of the proteasome (Joshi et al 2011). Irisflorentin, an isoflavone isolated from the roots of the traditional Chinese herbal, Belamcanda chinensis , was shown to specifically upregulate rpn-3 expression, which directly increased the chymotrypsin-like activity of the proteasome (Chen et al 2015). The increased proteasome activity led to decreased alpha-synuclein accumulation and decreased toxicity in a nematode model of Parkinson’s disease.…”
Section: Resultsmentioning
confidence: 99%
“…Proper RPN-3 levels are critical for proteasome function as either overexpression or deletion of rpn-3 disrupted the function of the proteasome (Joshi et al 2011). Irisflorentin, an isoflavone isolated from the roots of the traditional Chinese herbal, Belamcanda chinensis , was shown to specifically upregulate rpn-3 expression, which directly increased the chymotrypsin-like activity of the proteasome (Chen et al 2015). The increased proteasome activity led to decreased alpha-synuclein accumulation and decreased toxicity in a nematode model of Parkinson’s disease.…”
Section: Resultsmentioning
confidence: 99%
“…The phenolic groups enhance curcumin interactions with α-syn monomers as well as oligomers. In PC12 cells transfected with recombinant plasmids, α-syn-pEGFP-A53T downregulated α-syn expression or oligomer formation by regulating apoptosis-mediated mitochondrial membrane potential (Chen et al, 2015a ). The effect of curcumin on α-syn observed in vitro was reconfirmed in vivo in genetic mouse models of synucleinopathy (Spinelli et al, 2015 ).…”
Section: Phytochemicals Targeting α-Synuclein Assembly and Toxicitymentioning
confidence: 99%
“…CAT-2 overexpression confers resistance to 6-OHDA in wild-type and CAT-2 mutant backgrounds possibly due to reduced 6-OHDA uptake into dopaminergic neurons when excess dopamine is present (Masoudi et al, 2014 ). Due to the conservation between mammalian and C. elegans dopamine receptors, these and other results from toxin-induced neurodegeneration studies in C. elegans may help shed light on novel mechanisms leading to dopaminergic neuroprotection (Chen Y. M. et al, 2015 ).…”
Section: Caenorhabditis Elegans Models Of Parkinson's Diseasmentioning
confidence: 99%
“…To model α-synuclein aggregation and accumulation in vivo , researchers have generated transgenic C. elegans strains that express the human α-synuclein gene in body wall muscle cells and in neurons (Table 1 ). In these models, increased or decreased fluorescence intensity associated with YFP linked to α-synuclein can be quantified to determine the levels of protein expression (Jadiya et al, 2011 ; Jadiya and Nazir, 2012 ; Fatima et al, 2014 ; Fu et al, 2014a ; Chen Y. M. et al, 2015 ; Liu et al, 2015 ). Loss of fluorescence intensity indicates reduced protein expression, whereas increased fluorescence indicates increased α-synuclein expression.…”
Section: Markers Of Pathology In Genetic and Toxin-induced Pd mentioning
confidence: 99%