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image of Recent Advances in Co-Condensation and Co-Aggregation of Amyloid Proteins Linked to Neurodegenerative Diseases

Abstract

The misfolding and aggregation of amyloid proteins are closely associated with a range of neurodegenerative diseases. Liquid-liquid phase separation (LLPS) can initiate the aggregation of proteins, indicating that LLPS may serve as an alternative pathway for the pathological aggregation of amyloid proteins. The co-occurrence of two or more amyloid pathologies has been observed in extensive pathophysiological studies and is linked to faster disease progression. The co-LLPS (also known as co-condensation) and co-aggregation of different disease-related proteins have been proposed as a potential molecular mechanism for combined neuropathology. Here, we reviewed the current state of knowledge regarding the co-aggregation and co-condensation of various amyloid proteins, including Aβ, tau, α-synuclein, TDP-43, FUS, and hnRNPA/B protein family, C9orf72 dipeptide repeats and prion protein. We briefly introduced the epidemiological correlation among different neurodegenerative diseases and specifically presented recent experimental findings about co-aggregation and co-condensation of two different amyloid proteins. Additionally, we discussed computational studies focusing on the molecular interactions between amyloid proteins to offer mechanistic insights into the co-LLPS and co-aggregation processes. This review provides an overview of the synergistic interactions between different disease-related proteins, which is helpful for understanding the mechanisms of combined neuropathology and developing targeted therapeutic strategies.

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2025-02-10
2025-05-19

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Recent Advances in Co-Condensation and Co-Aggregation of Amyloid Proteins Linked to Neurodegenerative Diseases
Bentham Science Publishers ; https://doi.org/10.2174/0113892037350729241129054701
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  • Article Type:     Review Article
Keywords: co-condensation ; Neurodegenerative diseases ; molecular mechanism ; co-aggregation ; cross-seeding ; liquid-liquid phase separation ; amyloid proteins

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