Response of Silybum marianum plant to irrigation intervals combined with fertilization

Hendawy SF, Hussein MS, Youssef AA, El-Mergawi RA. 2013. Response of Silybum marianum plant to irrigation intervals combined with fertilization. Nusantara Bioscience 5: 21-28. This study was investigated to evaluate the influence of different kinds of organic and bio fertilization under different irrigation intervals on the growth, production and chemical constituents of Sylibium marianum plant. Data indicated that all studied growth and yield characters were significantly affected by the duration of irrigation intervals. Fertilizer treatments had a primitive effect on growth and yield characters. The interaction between irrigation intervals and fertilizer treatments has a clear considerable effect on growth and yield characters. The obtained results indicated the favorable effect of organic and bio fertilizers which reduce the harmful effect of water stress. Different treatments had a pronounced effect on silymarin content

SUMOylation and ubiquitination reciprocally regulate α-synuclein degradation and pathological aggregation

α-Synuclein accumulation is a pathological hallmark of Parkinson’s disease (PD). Ubiquitinated α-synuclein is targeted to proteasomal or lysosomal degradation. Here, we identify SUMOylation as a major mechanism that counteracts ubiquitination by different E3 ubiquitin ligases and regulates α-synuclein degradation. We report that PIAS2 promotes SUMOylation of α-synuclein, leading to a decrease in α-synuclein ubiquitination by SIAH and Nedd4 ubiquitin ligases, and causing its accumulation and aggregation into inclusions. This was associated with an increase in α-synuclein release from the cells. A SUMO E1 inhibitor, ginkgolic acid, decreases α-synuclein levels by relieving the inhibition exerted on α-synuclein proteasomal degradation. α-Synuclein disease mutants are more SUMOylated compared with the wild-type protein, and this is associated with increased aggregation and inclusion formation. We detected a marked increase in PIAS2 expression along with SUMOylated α-synuclein in PD brains, providing a causal mechanism underlying the up-regulation of α-synuclein SUMOylation in the disease. We also found a significant proportion of Lewy bodies in nigral neurons containing SUMO1 and PIAS2. Our observations suggest that SUMOylation of α-synuclein by PIAS2 promotes α-synuclein aggregation by two mutually reinforcing mechanisms. First, it has a direct proaggregatory effect on α-synuclein. Second, SUMOylation facilitates α-synuclein aggregation by blocking its ubiquitin-dependent degradation pathways and promoting its accumulation. Therefore, inhibitors of α-synuclein SUMOylation provide a strategy to reduce α-synuclein levels and possibly aggregation in PD

On the Neuroprotective Effects of Naringenin: Pharmacological Targets, Signaling Pathways, Molecular Mechanisms, and Clinical Perspective

As a group of progressive, chronic, and disabling disorders, neurodegenerative diseases (NDs) affect millions of people worldwide, and are on the rise. NDs are known as the gradual loss of neurons; however, their pathophysiological mechanisms have not been precisely revealed. Due to the complex pathophysiological mechanisms behind the neurodegeneration, investigating effective and multi-target treatments has remained a clinical challenge. Besides, appropriate neuroprotective agents are still lacking, which raises the need for new therapeutic agents. In recent years, several reports have introduced naturally-derived compounds as promising alternative treatments for NDs. Among natural entities, flavonoids are multi-target alternatives affecting different pathogenesis mechanisms in neurodegeneration. Naringenin is a natural flavonoid possessing neuroprotective activities. Increasing evidence has attained special attention on the variety of therapeutic targets along with complex signaling pathways for naringenin, which suggest its possible therapeutic applications in several NDs. Here, in this review, the neuroprotective effects of naringenin, as well as its related pharmacological targets, signaling pathways, molecular mechanisms, and clinical perspective, are described. Moreover, the need to develop novel naringenin delivery systems is also discussed to solve its widespread pharmacokinetic limitation