Defining a Lewy Body: Running Up the Hill of Shifting Definitions and Evolving Concepts

Journal of Parkinson s Disease, Год журнала: 2024, Номер 14(1), С. 17 - 33

Опубликована: Янв. 5, 2024

Lewy bodies (LBs) are pathological hallmarks of Parkinson’s disease and dementia with bodies, characterized by the accumulation α-synuclein (αSyn) protein in brain. While LBs were first described a century ago, their formation morphogenesis mechanisms remain incompletely understood. Here, we present historical overview LB definitions highlight importance semantic clarity precise when describing brain inclusions. Recent breakthroughs imaging revealed shared features within subsets enrichment membrane-bound organelles these structures, challenging conventional model. We discuss involvement emerging concepts liquid-liquid phase separation, where biomolecules demix from solution to form dense condensates, as potential mechanism. Finally, emphasize need for operational based on morphological characteristics detection protocols, particularly studies investigating mechanisms. A better understanding organization ultrastructure can contribute development targeted therapeutic strategies synucleinopathies.

Язык: Английский

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Transient, nano-scale, liquid-like molecular assemblies coming of age

Current Opinion in Cell Biology, Год журнала: 2024, Номер 89, С. 102394 - 102394

Опубликована: Июль 3, 2024

This review examines the dynamic mechanisms underlying cellular signaling, communication, and adhesion via transient, nano-scale, liquid-like molecular assemblies on plasma membrane (PM). Traditional views posit that stable, solid-like complexes perform these functions. However, advanced imaging reveals many signaling scaffolding proteins only briefly reside in micron-scale protein PM, including cell structures synapses, are likely made of archipelagoes nanoliquid islands. Borrowing concept liquid–liquid phase separation to form biocondensates, we propose nano-scale oligomers enabled by multiple weak but specific interactions often involving intrinsically disordered regions. The signals from individual would occur as pulses. Single-molecule emerges a crucial technique for characterizing transient suggesting shift toward model where fluidity underpins signal regulation integration.

Язык: Английский

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The emerging roles of the endoplasmic reticulum in mechanosensing and mechanotransduction

Journal of Cell Science, Год журнала: 2025, Номер 138(4)

Опубликована: Фев. 15, 2025

ABSTRACT Cells are continuously subjected to physical and chemical cues from the extracellular environment, sense respond mechanical via mechanosensation mechanotransduction. Although role of cytoskeleton in these processes is well known, contribution intracellular membranes has been long neglected. Recently, it become evident that various organelles play active roles both mechanosensing In this Review, we focus on mechanosensitive endoplasmic reticulum (ER), functions which crucial for maintaining cell homeostasis. We discuss effects stimuli interactions between ER, other organelles; ER Ca2+ signalling channels; how unfolded protein response lipid homeostasis contribute mechanosensing. The expansive structure positions as a key communication hub, additionally explore may be leveraged transduce signals around cell. By synthesising current knowledge, aim shed light emerging cellular

Язык: Английский

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Transmembrane signaling through single-spanning receptors modulated by phase separation at the cell surface

European Journal of Cell Biology, Год журнала: 2024, Номер 103(2), С. 151413 - 151413

Опубликована: Апрель 12, 2024

A wide variety of transmembrane signals are transduced by cell-surface receptors that activate intracellular signaling molecules. In particular, receptor clustering in the plasma membrane plays a critical role these processes. Single-spanning or single-pass proteins among most significant types receptors, which include adhesion such as integrins, CD44, cadherins, and tyrosine kinases. Elucidating molecular mechanisms underlying regulation activity is great significance. Liquid–liquid phase separation (LLPS) recently emerging paradigm cellular physiology for ubiquitous spatiotemporal dynamics various pathways. This study describes features through single-spanning from perspective separation. Possible physicochemical modulations LLPS-based also discussed.

Язык: Английский

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Aberrant tau condensates as catalytic microcompartments propel tau fibrillation

Structure, Год журнала: 2024, Номер 32(10), С. 1547 - 1549

Опубликована: Окт. 1, 2024

Язык: Английский

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