α-Synuclein interacts with lipoproteins in plasma

Parkinson’s disease (PD) is an age-related neurodegenerative disorder characterized by dopaminergic neural cell death in the substantia nigra of the brain and α-synuclein (α-syn) accumulation in Lewy bodies. α-Syn can be detected in blood and is a potential biomarker for PD. It has been shown recently that α-syn can pass through the blood-brain barrier (BBB), but the mechanism is not yet understood. We hypothesized that α-syn could interact with lipoproteins, and in association with these particles, could pass through the BBB. Here, we show that apoE, apoJ, and apoA1, but not apoB, were co-immunocaptured along with α-syn from human blood plasma, suggesting that α-syn is associated with high density lipoproteins (HDL). This association was also supported by experiments involving western blotting of plasma fractions separated by gel filtration,which revealed that α-syn was found in fractions identified as HDL. Interestingly, we could also detect α-syn and ApoJ in the intermediate fraction between HDL and LDL, referred to as lipoprotein (a) (Lp(a)), which has an important role in cholesterol metabolism. Overall, the results provide best support for the hypothesis that α-syn interacts with HDL, and this has potential implications for transport of α-syn from the brain to peripheral blood, across the BBB

Effects of different isoforms of apoE on aggregation of the α‐synuclein protein implicated in Parkinson’s disease

Parkinson’s disease is a progressive brain disorder due to the degeneration of dopaminergic neurons in the substantia nigra. The accumulation of aggregated forms of α-synuclein protein into Lewy bodies is one of the characteristic features of this disease although the pathological role of any such protein deposits in causing neurodegeneration remains elusive. Here, the effects of different apolipoprotein E isoforms (apoE2, apoE3, apoE4) on the aggregation of α-synuclein in vitro were examined using thioflavin T assays and also an immunoassay to detect the formation of multimeric forms. Our results revealed that the aggregation of α-synuclein is influenced by apoE concentration. At low concentrations of apoE (15 nM) of these isoforms, where a decrease in the aggregation of α-synuclein was noted. The data show that exceptionally low levels of apoE may seed α-syn aggregation, which could potentially lead to the pathogenesis of α‐synuclein-induced neurodegeneration. On the other hand, higher levels of apoE could potentially lower the degree of α-synuclein aggregation and confer protection. The differential effects noted with apoE4 could explain why this particular isoform results in an earlier age of onset for Parkinson’s disease

Association between polymorphisms of exon 12 and exon 24 of JHDM2A gene and male infertility

Background: Some dynamic changes occurs during spermatogenesis such as histone removal and its replacement with transition nuclear protein and protamine. These proteins are required for packing and condensation of sperm chromatin. JHDM2A is a histone demethylase that directly binds to promoter regions of Tnp1 and Prm1 genes and controls their expression by removing H3K9 at their promoters. Objective: The association between polymorphisms of exon 12 and exon 24 in JHDM2A gene and male infertility were evaluated for the first time. Materials and Methods: In this experimental study, 400 infertile men (oligospermia and azoospermia) and normal healthy fathers were evaluated (n=200). Single Strand Conformation Polymorphism (SSCP-PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods were used for screening any polymorphisms that are exist in exon 12 and exon 24. Results: Exon 24 PCR products were analyzed by RFLP but no polymorphism was found in this exon at the restriction site of EcoRV enzyme. Our monitoring along the whole nucleotides of exon 12 and exon 24 were continued using SSCP method, but we found no change along these exons. Conclusion: Generally, this study evaluated the association between polymorphisms in exon 12 and exon 24 of JHDM2A gene and male infertility which suggests that polymorphisms of these exons may not be associated with the risk of male infertility

Amyloidosis and Longevity: A Lesson from Plants

The variety of lifespans of different organisms in nature is amazing. Although it is acknowledged that the longevity is determined by a complex interaction between hereditary and environmental factors, many questions about factors defining lifespan remain open. One of them concerns a wide range of lifespans of different organisms. The reason for the longevity of certain trees, which reaches a thousand years and exceeds the lifespan of most long living vertebrates by a huge margin is also not completely understood. Here we have discussed some distinguishing characteristics of plants, which may explain their remarkable longevity. Among them are the absence (or very low abundance) of intracellular inclusions composed of amyloidogenic proteins, the lack of certain groups of proteins prone to aggregate and form amyloids in animals, and the high level of compounds which inhibit protein aggregation and possess antiaging properties

Cell Responses to Extracellular α-Synuclein

Synucleins are small naturally unfolded proteins involved in neurodegenerative diseases and cancer. The family contains three members: α-, β-, and -synuclein. α-Synuclein is the most thoroughly investigated because of its close association with Parkinson's disease (PD), dementia with Lewy bodies and multiple system atrophy. Until recently, the synuclein's research was mainly focused on their intracellular forms. However, new studies highlighted the important role of extracellular synucleins. Extracellular forms of synucleins propagate between various types of cells, bind to cell surface receptors and transmit signals, regulating numerous intracellular processes. Here we give an update of the latest results about the mechanisms of action of extracellular synucleins, their binding to cell surface receptors, effect on biochemical pathways and the role in neurodegeneration and neuroinflammation