alpha-synuclein and trans-sodium-crocetinate

Parkinson's disease (PD) is a common neurodegenerative disorder with motor symptoms linked to the loss of dopaminergic neurons in the brain. α-Synuclein is an aggregation-prone neural protein that plays a role in the pathogenesis of PD. In our previous paper, we found that saffron; the stigma of Crocus sativus Linné (Iridaceae), and its constituents (crocin and crocetin) suppressed aggregation of α-synuclein and promoted the dissociation of α-synuclein fibrils in vitro. In this study, we investigated the effect of dietary saffron and its constituent, crocetin, in vivo on a fly PD model overexpressing several mutant α-synuclein in a tissue-specific manner. Saffron and crocetin significantly suppressed the decrease of climbing ability in the Drosophila overexpressing A30P (A30P fly PD model) or G51D (G51D fly PD model) mutated α-synuclein in neurons. Saffron and crocetin extended the life span in the G51D fly PD model. Saffron suppressed the rough-eyed phenotype and the dispersion of the size histogram of the ocular long axis in the eye of A30P fly PD model. Saffron had a cytoprotective effect on a human neuronal cell line with α-synuclein fibrils. These data showed that saffron and its constituent crocetin have protective effects on the progression of PD disease in animals in vivo and suggest that saffron and crocetin can be used to treat PD.

Topics: alpha-Synuclein; Animals; Animals, Genetically Modified; Carotenoids; Cell Line; Crocus; Disease Models, Animal; Drosophila melanogaster; Female; Humans; Longevity; Male; Motor Activity; Mutation; Neurons; Neuroprotective Agents; Parkinson Disease; Retinal Degeneration; Vitamin A

Saffron, the stigma of Crocus sativus Linné (Iridaceae family), has been known to inhibit aggregation of β-amyloid, a nerve tissue protein. α-Synuclein (αS) is a 140-amino acid protein found abundantly in various regions of the brain. Its abnormal aggregation and accumulation in nerve tissue are said to cause neurodegenerative diseases such as Parkinson's disease, Lewy body dementia, and multiple-system atrophy. This study (part of this study was presented at the 137th Annual Meeting of the Pharmaceutical Society of Japan) examined the effects of saffron, its constituents (crocin-1, crocin-2, crocetin, and safranal), and crocetin structural analogs (hexadecanedioic acid, norbixin, and trans, trans-muconic acid) on αS aggregation, and αS fibril dissociation. Saffron dose-dependently inhibited αS aggregation and dissociated αS fibrils by thioflavin T fluorescence assay. These effects were observed by transmission electron microscopy, which showed reduced and shortened αS fibrils. Crocin-1, crocin-2, and crocetin showed anti-aggregation and fibril dissociation effects, with crocetin being the most potent. The effects of norbixin were weaker than those of crocetin, and the other crocetin structural analogs showed no effects. These results show that saffron and its constituents (crocin-1, crocin-2, and crocetin) can be effective in preventing and treating diseases caused by abnormal αS aggregation.

Topics: alpha-Synuclein; Carotenoids; Crocus; Plant Extracts; Vitamin A