Intrinsically disordered proteins and proteins with intrinsically disordered regions in neurodegenerative diseases

被引:35
|
作者
Coskuner-Weber, Orkid [1 ]
Mirzanli, Ozan [1 ]
Uversky, Vladimir N. [2 ]
机构
[1] Turkish German Univ, Mol Biotechnol, Sahinkaya Caddesi 106, TR-34820 Istanbul, Turkey
[2] Univ S Florida, USF Hlth Byrd Alzheimers Res Inst, Morsani Coll Med, Tampa, FL USA
关键词
Intrinsically disordered proteins; Proteins with intrinsically disordered regions; Neurodegeneration; Pathology; Drug design; MOLECULAR RECOGNITION FEATURES; POSITIVE ALLOSTERIC MODULATORS; ALPHA-SYNUCLEIN PROTEIN; FREE-ENERGY LANDSCAPES; COUPLED RECEPTORS; ALZHEIMERS-DISEASE; WILD-TYPE; PHYSIOLOGICAL FUNCTIONS; PARKINSONS-DISEASE; BINDING REGIONS;
D O I
10.1007/s12551-022-00968-0
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
Many different intrinsically disordered proteins and proteins with intrinsically disordered regions are associated with neurodegenerative diseases. These types of proteins including amyloid-& beta;, tau, & alpha;-synuclein, CHCHD2, CHCHD10, and G-protein coupled receptors are increasingly becoming evaluated as potential drug targets in the pharmaceutical-based treatment approaches. Here, we focus on the neurobiology of this class of proteins, which lie at the center of numerous neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, Huntington's disease, amyotrophic lateral sclerosis, frontotemporal dementia, Charcot-Marie-Tooth diseases, spinal muscular atrophy, and mitochondrial myopathy. Furthermore, we discuss the current treatment design strategies involving intrinsically disordered proteins and proteins with intrinsically disordered regions in neurodegenerative diseases. In addition, we emphasize that although the G-protein coupled receptors are traditionally investigated using structural biology-based models and approaches, current studies show that these receptors are proteins with intrinsically disordered regions and therefore they require new ways for their analysis.
引用
收藏
页码:679 / 707
页数:29
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