Modulation of biomolecular phase behavior by metal ions

Sołtys, Katarzyna; Tarczewska, Aneta; Bystranowska, Dominika

doi:10.1016/j.bbamcr.2023.119567

Cited by 3 publications

(3 citation statements)

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“…Metal Ion: The determination of metal ion concentrations represents a significant area of exploration. Maintaining appropriate ion concentrations both inside and outside cells is crucial for the normal physiological functioning of organisms [ [263] , [264] , [265] ]. The detection of such substrates typically hinges on the redox properties of metal ions, which lead to the formation of metal complexes and chelates in solution systems.…”

Section: Sensing and Detectionmentioning

confidence: 99%

Semiconducting polymer dots for multifunctional integrated nanomedicine carriers

Zhang,

Yu,

et al. 2024

Materials Today Bio

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Section: Sensing and Detectionmentioning

confidence: 99%

Semiconducting polymer dots for multifunctional integrated nanomedicine carriers

Zhang,

Yu,

et al. 2024

Materials Today Bio

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“…The similarity between each of these ALS associated proteins is that they all undergo LLPS, including SOD1 ( Gu et al, 2023 ). This is because intrinsically disordered domain-containing proteins are naturally susceptible to aggregation ( Ayyadevara et al, 2022 ), and also to metal ion-included LLPS ( Sołtys et al, 2023 ). In particular, copper and zinc can induce LLPS as seen in AD with both Aβ and Tau undergoing LLPS in response to metal ion-induced stress ( Fu et al, 2024 ).…”

Section: Metal Ions Llps and Co-aggregation Of Als Proteinsmentioning

confidence: 99%

Copper toxicity and deficiency: the vicious cycle at the core of protein aggregation in ALS

Min,

Sarlus,

Harris

2024

Front. Mol. Neurosci.

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The pathophysiology of ALS involves many signs of a disruption in copper homeostasis, with both excess free levels and functional deficiency likely occurring simultaneously. This is crucial, as many important physiological functions are performed by cuproenzymes. While it is unsurprising that many ALS symptoms are related to signs of copper deficiency, resulting in vascular, antioxidant system and mitochondrial oxidative respiration deficiencies, there are also signs of copper toxicity such as ROS generation and enhanced protein aggregation. We discuss how copper also plays a key role in proteostasis and interacts either directly or indirectly with many of the key aggregate-prone proteins implicated in ALS, such as TDP-43, C9ORF72, SOD1 and FUS as well as the effect of their aggregation on copper homeostasis. We suggest that loss of cuproprotein function is at the core of ALS pathology, a condition that is driven by a combination of unbound copper and ROS that can either initiate and/or accelerate protein aggregation. This could trigger a positive feedback cycle whereby protein aggregates trigger the aggregation of other proteins in a chain reaction that eventually captures elements of the proteostatic mechanisms in place to counteract them. The end result is an abundance of aggregated non-functional cuproproteins and chaperones alongside depleted intracellular copper stores, resulting in a general lack of cuproenzyme function. We then discuss the possible aetiology of ALS and illustrate how strong risk factors including environmental toxins such as BMAA and heavy metals can functionally behave to promote protein aggregation and disturb copper metabolism that likely drives this vicious cycle in sporadic ALS. From this synthesis, we propose restoration of copper balance using copper delivery agents in combination with chaperones/chaperone mimetics, perhaps in conjunction with the neuroprotective amino acid serine, as a promising strategy in the treatment of this incurable disease.

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“…47,48 Interestingly, neurodegenerative disease-promoting factors such as familial mutations, gene multiplication, post-translational modification, metal ions exposure, oxidative stress, DNA damage, and the presence of RNA also facilitate phase separation events and subsequent viscoelastic liquid-to-solid transition. 49–55 Since the nucleation event is the rate-limiting step for amyloid aggregation, 56 it is reasonable to hypothesize that these factors may modulate LLPS and subsequent amyloid nucleation from condensates. Indeed, the amyloid aggregation pathway preceded by LLPS is emerging as a common aggregation mechanism for various neurodegenerative disease-associated proteins apart from the traditional pathway of amyloid aggregation from the bulk solution.…”

Section: Introductionmentioning

confidence: 99%

Protein misfolding and amyloid nucleation through liquid–liquid phase separation

Mukherjee,

Poudyal,

Dave

et al. 2024

Chem. Soc. Rev.

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Modulation of biomolecular phase behavior by metal ions

Cited by 3 publications

References 205 publications

Semiconducting polymer dots for multifunctional integrated nanomedicine carriers

Semiconducting polymer dots for multifunctional integrated nanomedicine carriers

Copper toxicity and deficiency: the vicious cycle at the core of protein aggregation in ALS

Protein misfolding and amyloid nucleation through liquid–liquid phase separation

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