Aberrant liquid-liquid phase separation and amyloid aggregation of proteins related to neurodegenerative diseases

被引:30
作者
Ahmad, Azeem [1 ]
Uversky, Vladimir N. [2 ,3 ]
Khan, Rizwan Hasan [1 ]
机构
[1] Aligarh Muslim Univ, Interdisciplinary Biotechnol Unit, Aligarh 202002, UP, India
[2] Univ S Florida, Byrd Alzheimers Res Inst, Morsani Coll Med, Dept Mol Med, Tampa, FL 33612 USA
[3] Moscow Inst Phys & Technol, Res Ctr Mol Mech Aging & Age Related Dis, Inst Pereulok 9, Dolgoprudnyi 141700, Russia
关键词
Liquid -liquid phase separation; Liquid -solid transition; Membrane -less organelles; Biomolecular condensates; PRION-LIKE DOMAINS; INTRINSICALLY DISORDERED PROTEINS; RNA-BINDING PROTEINS; AMYOTROPHIC-LATERAL-SCLEROSIS; ALPHA-SYNUCLEIN; MUTANT HUNTINGTIN; POSTTRANSLATIONAL MODIFICATIONS; MICROTUBULE-BINDING; STRESS GRANULES; REPEAT LENGTH;
D O I
10.1016/j.ijbiomac.2022.08.132
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Recent evidence has shown that the processes of liquid-liquid phase separation (LLPS) or liquid-liquid phase transitions (LLPTs) are a crucial and prevalent phenomenon that underlies the biogenesis of numerous membrane-less organelles (MLOs) and biomolecular condensates within the cells. Findings show that processes associated with LLPS play an essential role in physiology and disease. In this review, we discuss the physical and biomolecular factors that contribute to the development of LLPS, the associated functions, as well as their consequences for cell physiology and neurological disorders. Additionally, the finding of mis-regulated proteins, which have long been linked to aggregates in neuropathology, are also known to induce LLPS/LLPTs, prompting a lot of interest in understanding the connection between aberrant phase separation and disorder conditions. Moreover, the methods used in recent and ongoing studies in this field are also explored, as is the possibility that these findings will encourage new lines of inquiry into the molecular causes of neurodegenerative diseases.
引用
收藏
页码:703 / 720
页数:18
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