The novel anti-fibrillary effects of volatile compounds α-asarone and ß-caryophyllene on tau protein: Towards promising therapeutic agents for Alzheimer's disease.

The abnormal deposition of tau protein is one of the critical causes of tauopathies including Alzheimer's disease (AD). In recent years, there has been great interest in the use of essential oils and volatile compounds in aromatherapy for treating AD, since volatile compounds can directly reach the brain through intranasal administration. The volatile compounds α-asarone (ASA) and ß-caryophyllene (BCP) have revealed various important neuroprotective properties, useful in treating AD. In this study, the volatile compounds ASA and BCP were assessed for their effectiveness in preventing tau fibrillation, disassembly of pre-formed tau fibrils, and disaggregation of tau aggregates. SDS-PAGE and AFM analyses revealed that ASA and BCP inhibited tau fibrillation/aggregation and decreased the mean size of tau oligomers. Tau samples treated with ASA and BCP, showed a reduction in ThT and ANS fluorescence intensities, and a decrease in the ß-sheet content. Additionally, ASA and BCP disassembled the pre-formed tau fibrils to the granular and linear oligomeric intermediates. Treatment of neuroblastoma SH-SY5Y cells with tau samples treated with ASA and BCP, revealed protective effects as shown by reduced toxicity of the cells, due to the inhibition of tau fibrillation/aggregation. Overall, ASA and BCP appeared to be promising therapeutic candidates for AD.

Structural and functional alteration of human αA-crystallin after exposure to full spectrum solar radiation and preventive role of lens antioxidants.

The chronically exposure of eye lenses to ultra violet and visible light of the solar radiation is an important risk factor for development of the senile cataract diseases. Various photosensitizer molecules including riboflavin (RF) play a significant role in photo-oxidative damages of lens proteins underlying development of opacity in the lenticular tissues. In the current study, RF-mediated photo-oxidation of human αA-crystallin (αA-Cry) was assessed using SDS-PAGE analysis, dynamic light scattering and other spectroscopic assessments. The RF-photosensitized reactions led to non-disulfide covalent cross-linking, oligomerization and significant structural changes in αA-Cry. The photo-damaging of αA-Cry under solar radiation was also accompanied by the reduction in both Trp and Tyr fluorescence intensities which followed by the formation of new photosensitizer chromophores. The solvent exposed hydrophobic patches, secondary structures and chaperone-like activity of αA-Cry were significantly altered after exposure to the solar radiation in the presence of RF. Although glutathione and ascorbate were capable to partially protect the photo-induced structural damages of human αA-Cry, they also disrupted its chaperone function when co-exposed with this protein to the solar radiation. Also, the most promising data were obtained with cysteine which its availability in the lenticular tissues is a rate limiting factor for the biosynthesis of glutathione. Overall our results suggest that glutathione and ascorbate, as the major anti-oxidant compounds within lenticular tissues, demonstrate controversial effect on structure and chaperone-like activity of human αA-Cry. Elucidation of this effect may demand further experiments.

Preventive role of lens antioxidant defense mechanism against riboflavin-mediated sunlight damaging of lens crystallins.

The main components of sunlight reaching the eye lens are UVA and visible light exerting their photo-damaging effects indirectly by the aid of endogenous photosensitizer molecules such as riboflavin (RF). In this study, lens proteins solutions were incubated with RF and exposed to the sunlight. Then, gel mobility shift analysis and different spectroscopic assessments were applied to examine the structural damaging effects of solar radiation on these proteins. Exposure of lens proteins to direct sunlight, in the presence of RF, leads to marked structural crosslinking, oligomerization and proteolytic instability. These structural damages were also accompanied with reduction in the emission fluorescence of Trp and Tyr and appearance of a new absorption peak between 300 and 400nm which can be related to formation of new chromophores. Also, photo-oxidation of lens crystallins increases their oligomeric size distribution as examined by dynamic light scattering analysis. The above mentioned structural insults, as potential sources of sunlight-induced senile cataract and blindness, were significantly attenuated in the presence of ascorbic acid and glutathione which are two important components of lens antioxidant defense system. Therefore, the powerful antioxidant defense mechanism of eye lens is an important barrier against molecular photo-damaging effects of solar radiations during the life span.