From structure to ætiology: a new window on the biology of leucine-rich repeat kinase 2 and Parkinson's disease
| Autor: | Susanne Herbst, Patrick A. Lewis |
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| Rok vydání: | 2021 |
| Předmět: |
Models
Molecular Time Factors Parkinson's disease Cell Computational biology Disease Biology Leucine-rich repeat Crystallography X-Ray Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 Biochemistry Molecular Bases of Health & Disease 03 medical and health sciences leucine-rich repeat kinase 0302 clinical medicine Protein Domains Structural Biology medicine Humans Genetic Predisposition to Disease Protein Kinase Inhibitors Molecular Biology 030304 developmental biology 0303 health sciences Kinase Cryoelectron Microscopy Neurodegeneration neurodegeneration Parkinson Disease Cell Biology medicine.disease LRRK2 In vitro nervous system diseases medicine.anatomical_structure Mutation Perspective Biocatalysis Translational Science Protein Multimerization 030217 neurology & neurosurgery Signal Transduction Neuroscience |
| Zdroj: | Biochemical Journal |
| ISSN: | 1470-8728 0264-6021 |
| Popis: | Since the discovery of mutations in leucine-rich repeat kinase 2 (LRRK2) as an underlying genetic cause for the development of Parkinson's disease (PD) in 2004 (Neuron 44, 601–607; Neuron 44, 595–600), and subsequent efforts to develop LRRK2 kinase inhibitors as a therapy for Parkinson's (Expert Opin. Ther. Targets 21, 751–753), elucidating the atomic resolution structure of LRRK2 has been a major goal of research into this protein. At over 250 kDa, the large size and complicated domain organisation of LRRK2 has made this a highly challenging target for structural biologists, however, a number of recent studies using both in vitro and in situ approaches (Nature 588, 344–349; Cell 182, 1508–1518.e1516; Cell 184, 3519–3527.e3510) have provided important new insights into LRRK2 structure and the complexes formed by this protein. |
| Databáze: | OpenAIRE |
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