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Huntington's disease (HD) is the most common inherited neurodegenerative disorder among polyglutamine (polyQ) diseases caused by cytosine-adenine-guanine repeat expansion in exon 1 of the huntingtin gene whose translation results in polyQ stretch in the N-terminus of the huntingtin protein (HD protein). This mutation significantly affects huntingtin conformation, proteolysis, PTMs, as well as its ability to bind interacting proteins. As a consequence, a variety of cellular mechanisms such as transcription, mitochondrial energy metabolism, axonal transport, neuronal vulnerability to oxidative stress, neurotransmission, and immune response are altered and involved in the pathogenesis of HD. Promising candidate molecular biomarkers of HD have emerged from proteomic studies. Recent analyses focused on HD protein itself, its PTM, and interacting proteins, which are of great importance for disease course. Furthermore, brain, body fluids, and immune system are intensively studied in order to search for additional proteins with a view to their use as a biomarker(s) or set of biomarkers in clinical trials in HD translational research.

Neurodegenerative diseases are devastating disorders and the demands on their treatment are set to rise in connection with higher disease incidence. Knowledge of the spatiotemporal profile of cellular protein expression during neural differentiation and definition of a set of markers highly specific for targeted neural populations is a key challenge. Intracellular proteins may be utilized as a readout for follow-up transplantation and cell surface proteins may facilitate isolation of the cell subpopulations, while secreted proteins could help unravel intercellular communication and immunomodulation. This review summarizes the potential of proteomics in revealing molecular mechanisms underlying neural differentiation of stem cells and presents novel candidate proteins of neural subpopulations, where understanding of their functionality may accelerate transition to cell replacement therapies.

Backgroundβ-catenin is a key component of Wnt signalling pathway which controls brain development and neurogenesis of the adult brain. Within a cell, β-catenin is continuously synthesised and its level is strictly regulated by phosphorylation and subsequent degradation via ubiquitin-proteasome system. Recently, the accumulation of β-catenin has been associated with Huntington disease as a consequence of the impaired degradation caused by mutated huntingtin.AimsOur study is aimed at monitoring β-catenin level in minipigs transgenic for the N-terminal part of human mutated huntingtin, the model developed in our institute.MethodsUsing Western blot and specific antibodies, transgenic animals and their siblings of the same age and the identical genetic background were examined for the expression of β-catenin. Furthermore, phosphorylation of β-catenin was monitored applying the method of phosphoprotein isolation. Finally, β-catenin was isolated by immunoprecipitation and subjected to mass-spectrometric analysis.ResultsTwo forms of β-catenin with minimal variance in molecular weight were detected in all samples from transgenic and wild-type pigs. Although there were no significant differences in β-catenin of the lower molecular weight, a noticeable decrease of heavier form was observed in transgenic animals. More interestingly, β-catenin of lower molecular weight was substantially phosphorylated suggesting that such modification is not responsible for the presence of heavier β-catenin in control animals. In order to reveal the differences among two observed forms of β-catenin, immunoprecipitation followed by mass spectrometry was performed and results will be discussed.ConclusionOur results demonstrate the presence of two distinct forms of β-catenin and indicate that a specific form of the protein is almost absent in transgenic animals. We hope that in depth investigation of this protein will extend our knowledge about the pathophysiology of Huntington disease.