Parkinson’s disease (PD) is a progressive neurodegenerative disorder caused mainly by lack of dopamine in the brain. Dopamine is a neurotransmitter involved in movement, motivation, memory, and other functions; its level is decreased in PD brain as a result of dopaminergic cell death. Dopamine loss in PD brain is a cause of motor deficiency and, possibly, a reason of the cognitive deficit observed in some PD patients. PD is mostly not recognized in its early stage because of a long latency between the first damage to dopaminergic cells and the onset of clinical symptoms. Therefore, it is very important to find reliable molecular biomarkers that can distinguish PD from other conditions, monitor its progression, or give an indication of a positive response to a therapeutic intervention. PD biomarkers can be subdivided into four main types: clinical, imaging, biochemical, and genetic. For a long time protein biomarkers, dopamine metabolites, amino acids, etc. in blood, serum, cerebrospinal liquid (CSF) were considered the most promising. Among the candidate biomarkers that have been tested, various forms of α-synuclein (α-syn), i.e., soluble, aggregated, post-translationally modified, etc. were considered potentially the most efficient. However, the encouraging recent results suggest that microRNA-based analysis may bring considerable progress, especially if it is combined with α-syn data. Another promising analysis is the advanced metabolite profiling of body fluids, called “metabolomics” which may uncover metabolic fingerprints specific for various stages of PD. Conventional pharmacological treatment of PD is based on the replacement of dopamine using dopamine precursors (levodopa, L-DOPA, L-3,4 dihydroxyphenylalanine), dopamine agonists (amantadine, apomorphine) and MAO-B inhibitors (selegiline, rasagiline), which can be used alone or in combination with each other. Potential risk factors include environmental toxins, drugs, pesticides, brain microtrauma, focal cerebrovascular damage, and genomic defects. This review covers molecules that might act as the biomarkers of PD. Then, PD risk factors (including genetics and non-genetic factors) and PD treatment options are discussed.

At present, when a clinical diagnosis of Parkinson's disease (PD) is made, serious damage has already been done to nerve cells of the substantia nigra pars compacta. The diagnosis of PD in its earlier stages, before this irreversible damage, would be of enormous benefit for future treatment strategies designed to slow or halt the progression of this disease that possibly prevents accumulation of toxic aggregates. As a molecular biomarker for the detection of PD in its earlier stages, alpha-synuclein (α-syn), which is a key component of Lewy bodies, in which it is found in an aggregated and fibrillar form, has attracted considerable attention. Here, α-syn is reviewed in details.

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.

Synucleins are small naturally unfolded proteins involved in neurodegenerative diseases and cancer. The family contains three members: α-, β-, and γ-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.

Parkinson's disease is a progressive brain disorder due to the degeneration of dopaminergic neurons in the substantia nigra. Parkinson's disease is a progressive brain disorder due to the degeneration of dopaminergic neutrons in the SN. 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), all of the isoforms were able to increase the aggregation of α-synuclein (50 µM), with apoE4 showing the greatest stimulatory effect. This is in contrast to a higher concentration (>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.