Tau liquid–liquid phase separation in neurodegenerative diseases

Boyko, Solomiia; Surewicz, Witold K.

doi:10.1016/j.tcb.2022.01.011

Cited by 94 publications

(68 citation statements)

References 89 publications

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“…We can control the function of a biomolecular condensate by regulating its LLPS behaviors by changing the experimental conditions and/or the protein sequence by mutagenesis ( 41 , 46 , 47 ). In addition, LLPS has been implicated in neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases ( 16 , 18 , 48 , 49 ). It has been hypothesized that LLPS of the pathological proteins can accelerate their nucleation and consequent fibrillation ( 50 ).…”

Section: Recent Trends In Research Of Biomolecular Llpsmentioning

confidence: 99%

“…One of its implications is that the malfunction of LLPS can lead to a lethal disease. Particularly, the interplay between LLPS and fibrillation of pathological proteins for neurodegenerative diseases has attracted a lot of interest ( 16 ). Our understanding of the interplay may provide an insight into a new cure for neurodegenerative diseases, which are considered almost incurable for now.…”

Section: Recent Trends In Research Of Biomolecular Llpsmentioning

confidence: 99%

“…LLPS is also observed in many processes such as miRISC assembly ( 10 ), innate immune signalling ( 11 ), stress granule assembly ( 12 ), autophagy ( 13 ), nucleolus formation ( 14 ), and transcription ( 15 ). In addition, LLPS even has implications for the pathogenesis of cancer and many neurodegenerative such as Alzheimer’s disease, Huntington’s disease, and amyotrophic lateral sclerosis ( 16 - 18 ).…”

Section: Introductionmentioning

confidence: 99%

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Recent trends in studies of biomolecular phase separation.

Kim¹,

Hwang²,

Kumar³

et al. 2022

BMB Rep

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Biomolecular phase separation has recently attracted broad in-terest, due to its role in the spatiotemporal compartmentalization of living cells. It governs the formation, regulation, and dissociation of biomolecular condensates, which play multiple roles in vivo , from activating specific biochemical reactions to organizing chromatin. Interestingly, biomolecular phase separation seems to be a mainly passive process, which can be ex-plained by relatively simple physical principles and reproduced in vitro with a minimal set of components. This Mini review focuses on our current understanding of the fundamental principles of biomolecular phase separation and the recent progress in the research on this topic.

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Section: Recent Trends In Research Of Biomolecular Llpsmentioning

confidence: 99%

Section: Recent Trends In Research Of Biomolecular Llpsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Recent trends in studies of biomolecular phase separation.

Kim¹,

Hwang²,

Kumar³

et al. 2022

BMB Rep

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“…At the same time, iron exposure to neuronal cultures overexpressing α -syn with familial mutation (A53T α -syn) increases the formation of aggregates and susceptibility to iron-induced toxicity [ 124 ]. Phosphorylated α -syn can reduce iron input through TfR endocytosis [ 125 ]. In neurons exposed to excess iron, overexpression of α -syn leads to increased intracellular iron levels and redistribution of iron from the cytoplasm to the perinuclear region in α -syn-rich inclusions [ 126 ].…”

Section: The Significance Of Llps-induced Protein Aggregation Caused ...mentioning

confidence: 99%

Liquid-Liquid Phase Separation Promotes Protein Aggregation and Its Implications in Ferroptosis in Parkinson’s Disease Dementia

Fan

et al. 2022

Oxidative Medicine and Cellular Longevity

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The pathological features of PDD are represented by dopaminergic neuronal death and intracellular α-synuclein (α-syn) aggregation. The interaction of iron accumulation with α-syn and tau was further explored as an essential pathological mechanism of PDD. However, the links and mechanisms between these factors remain unclear. Studies have shown that the occurrence and development of neurodegenerative diseases such as PDD are closely related to the separation of abnormal phases. Substances such as proteins can form droplets through liquid-liquid phase separation (LLPS) under normal physiological conditions and even undergo further liquid-solid phase transitions to form solid aggregates under disease or regulatory disorders, leading to pathological phenomena. By analyzing the existing literature, we propose that LLPS is the crucial mechanism causing abnormal accumulation of α-syn, tau, and other proteins in PDD, and its interaction with iron metabolism disorder is the key factor driving ferroptosis in PDD. Therefore, we believe that LLPS can serve as one of the means to explain the pathological mechanism of PDD. Determining the significance of LLPS in neurodegenerative diseases such as PDD will stimulate interest in research into treatments based on interference with abnormal LLPS.

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“…Besides, abnormal assembly of TAU and its solid phase accumulation are also involved in the development of neurodegenerative diseases (67). Phosphorylated free tau is mislocated and accumulates in dendrites and P10 www.biosciencetrends.com BioScience Trends Advance Publication somatic cells, which ultimately leads to the pathological features of neurodegenerative diseases (75). It has been demonstrated that aggregated TAU inhibits anterograde fast axonal transport, which supports the hypothesis that tau oligomers are toxic in neurodegenerative diseases and facilitates elucidation of the exact mechanism of tau-mediated neurotoxicity.…”

Section: Neurodegenerative Diseasesmentioning

confidence: 99%