Abstract:
:Aggregates of alpha-synuclein (αSyn) have been described in Parkinson's disease (PD) patients, and recent evidence has suggested that the most toxic αSyn species in PD are small soluble aggregates including oligomers, prefibrils, protofibrils. The physiological function of αSyn is still highly debated, with a possible role in synaptic vesicle trafficking and release at the presynaptic compartment, and in the regulation of gene expression in the nucleus. Emerging evidence indicate that most of αSyn functions are related with the crucial ability to bind biological membranes, which is associated with structural conversion from a disordered monomer to an α-helical enriched structure. Conformational properties of αSyn can be modulated by a number of factors including post-translational modifications, gene duplication and triplication-driven overexpression, single point mutations, environmental changes, which affect membrane binding and the protein propensity to aggregate in toxic species. The recognized toxic role of αSyn in PD has laid the rational for purposing of αSyn-based, neuropathologically relevant preclinical models of PD. Different approaches have led to the establishment of transgenic models, viral vector-based models, and more recently models based on the intracerebral inoculation of exogenous αSyn preformed fibrils/oligomers. Here, we overview and compare viral vector-based models of αSyn overexpression and models obtained by direct intracerebral infusion of in vitro preformed αSyn species. The advantages and pitfalls associated with these different approaches are discussed.
journal_name
J Neurosci Methodsjournal_title
Journal of neuroscience methodsauthors
Carta AR,Boi L,Pisanu A,Palmas MF,Carboni E,De Simone Adoi
10.1016/j.jneumeth.2020.108685subject
Has Abstractpub_date
2020-05-15 00:00:00pages
108685eissn
0165-0270issn
1872-678Xpii
S0165-0270(20)30107-2journal_volume
338pub_type
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journal_title:Journal of neuroscience methods
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journal_title:Journal of neuroscience methods
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journal_title:Journal of neuroscience methods
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journal_title:Journal of neuroscience methods
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journal_title:Journal of neuroscience methods
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journal_title:Journal of neuroscience methods
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