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Mol Neurobiol. 2018 Sep;55(9):7588-7605. doi: 10.1007/s12035-018-0926-y. Epub 2018 Feb 10.

Molecular and Clinical Aspects of Protein Aggregation Assays in Neurodegenerative Diseases.

Author information

1
Department of Neurology, University Medical Center Göttingen and German Center for Neurodegenerative Diseases, Robert-Koch-Str. 40, 37075, Göttingen, Germany. avillar@gwdg.de.
2
Department of Neurology, University Medical Center Göttingen and German Center for Neurodegenerative Diseases, Robert-Koch-Str. 40, 37075, Göttingen, Germany. matthias.schmitz@med.uni-goettingen.de.
3
Department of Neurology, University Medical Center Göttingen and German Center for Neurodegenerative Diseases, Robert-Koch-Str. 40, 37075, Göttingen, Germany.
4
Departament de Bioquímica i Biologia Molecular i Institut de Biotecnologia i Biomedicina, Universitat Autònoma de Barcelona, Barcelona, Spain.
5
Center for Networked Biomedical Research on Neurodegenerative Diseases - CIBERNED, Barcelona, Spain.

Abstract

The presence of protein deposits is a common pathological hallmark in patients suffering from neurodegenerative conditions and other proteinopathies. Deciphering the molecular basis of protein misfolding and aggregation is a crucial step towards the full comprehension of the factors that trigger the onset of these diseases and for the development of efficient therapeutical strategies. In this regard, in vitro aggregation assays for misfolded proteins offer an excellent tool to study pathological processes of protein deposition under controlled conditions, where confounders can be easily discriminated. These methods are generally cost-effective and have been proved useful in many fields, including drug discovery and clinical diagnostics. Here, we review the bases of in vitro aggregation and seeding assays, recapitulate their main applications and offer a critical evaluation of their limitations. Comprehending the molecular mechanisms behind these assays and combining them with in vivo or cell-based experiments will maximize their potential and allow the necessary improvement to overcome some of the current drawbacks.

KEYWORDS:

In vitro aggregation assays; Neurodegeneration; Prion; Protein misfolding; Seeding

PMID:
29429052
DOI:
10.1007/s12035-018-0926-y
[Indexed for MEDLINE]

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