中国神经再生研究(英文版) ›› 2024, Vol. 19 ›› Issue (5): 966-968.doi: 10.4103/1673-5374.382250

• 观点:退行性病与再生 • 上一篇    下一篇

磷酸化驱动的聚集蛋白在神经退行性疾病中的意义和治疗

  

  • 出版日期:2024-05-15 发布日期:2023-10-31

Phosphorylation-driven aggregative proteins in neurodegenerative diseases: implications and therapeutics

Alba Espargaró, Raimon Sabate*#br#

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  1. Department of Pharmacy and Pharmaceutical Technology and Physical-Chemistry, School of Pharmacy, University of Barcelona, Barcelona, Spain (Espargaró A, Sabate R) 
    Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, Barcelona, Spain (Espargaró A, Sabate R)
  • Online:2024-05-15 Published:2023-10-31
  • Contact: Raimon Sabate, PhD, rsabate@ub.edu.
  • Supported by:
    This work was funded by Ministerio de Ciencia e Innovación, Grant Number PID2021-127863OB-I00 (to AE and RS).

摘要: https://orcid.org/0000-0003-3894-2362 (Raimon Sabate)

Abstract: Protein aggregation is related to a large number of neurodegenerative disorders. Particularly in some cases, aggregation is induced by hyperphosphorylation of a given protein. This is the case of tau, TAR DNA-binding protein 43 (TDP-43), amyloid-beta peptides (Aβ) and alpha-synuclein (α-syn), which play a key pathogenic role in Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis, among others (Tenreiro et al., 2014; Chiti and Dobson, 2017). In this perspective, we will discuss both the relationship between phosphorylation and amyloid aggregation as well as current and future therapeutic strategies aimed at inhibiting specific kinases involved in the phosphorylation step or inhibiting subsequent protein aggregation. Moreover, we will address novel approaches that are based on chemical-inducing proximity, to recruit the proteasome, the autophagy-lysosome system or specific phosphatases to degrade or dephosphorylate the target proteins. We want to focus our interest on proteolysis-targeting chimeras (PROTACs) systems, which represent one of the newest and most interesting therapeutic approaches that could be applicable to phosphorylation-driven aggregative proteins in the near future (Ciechanover and Kwon, 2015; Esposto and Martic, 2021; Jangampalli et al., 2021; Jiang et al., 2021).