Chemical regulation of Tau oligomers in phase separation in Alzheimer’s disease
1 Institute of Chemical Biology and Functional Molecules, State Key Laboratory of Materials-Oriented Chemical Engineering, School of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing 211816, P. R. China.
2 School of Pharmaceutical science, Nanjing Tech University, Nanjing211816, China.
3 Department of Chemistry, Government Degree College No 2 Mardan, KPK, Pakistan.
4 Hubei provincial Center for disease Control and prevention, wuhan, China.
Review
World Journal of Biology Pharmacy and Health Sciences, 2024, 19(02), 380–390.
Article DOI: 10.30574/wjbphs.2024.19.2.0534
Publication history:
Received on 07 July 2024; revised on 22 August 2024; accepted on 24 August 2024
Abstract:
A huge number of patients suffering from certain neurodegenerative disorder, which are collectively called as tauopathies, may exhibit pathological tau protein aggregates in their brains. This category of diseases includes Alzheimer's disease (AD). In AD, post translational modifications such as phos phorylations, glycosylations, truncations, and subsequent aggregation into oligomers, paired helical filaments (PHFs), and neurofibrillary tangles (NFTs) are closely associated with cognitive decline and neurodegeneration. As a result, tau oligomers have emerged as the primary toxic species in AD and tauo pathies. Tau oligomers are soluble, self-assembled tau proteins that are formed prior to fibrils and have been demonstrated to play a pivotal role in neuronal cell death and the induction of neurodegeneration in animal models. In this succinct review, we collate and summarize literature pertaining to tau oligomer formation and its role in Alzheimer's disease. Secondly, we explore the crucial role of zinc ions (Zn²⁺) in tau aggregation, as studies suggest that zinc induces reversible tau oligomerization and can lead to tau hyper phosphorylation. The concentration of zinc is critical, as excessive levels can promote harmful tau aggregation, while normal levels are essential for physiological functions. We also examine natural and chemical compounds that can modulate tau aggregation, and lastly, we discuss how Tau protein can undergo liquid-liquid phase separation (LLPS) in neurons, forming droplets that can later develop into toxic oligomers, which are the primary hallmark of AD. We mention some molecules, such as proteins, nucleic acids, and metal ions, that influence tau LLPS and aggregation.
Keywords:
Alzheimer's Disease; Tau Protein; Oligomerization; Modulation; Zinc Ions; Liquid-Liquid Phase Separation (LLPS).
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