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Tau Pathobiology in Neurodegenerative Diseases: From Molecular Mechanisms to Therapeutic Advances

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: 15 July 2024 | Viewed by 586

Special Issue Editors


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Guest Editor
European Brain Research Institute (EBRI), Viale Regina Elena 295, 00161 Rome, Italy
Interests: tau protein; tau cleavage; amyloid beta; Alzheimer's disease, neurodegeneration; retina; eye degeneration; synaptotoxicity; immunotherapy; Nerve Growth Factor (NGF)
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
1. European Brain Research Institute (EBRI), Viale Regina Elena 295, 00161 Rome, Italy
2. Institute of Translational Pharmacology (IFT), National Research Council (CNR), Via Fosso del Cavaliere 100, 00133 Rome, Italy
Interests: tau protein; Alzheimer's disease (AD); amyloid beta; Amyloid Precursor Protein (APP); synapse; non-AD tauopathies; immunotherapy; neurodegeneration
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Alzheimer’s Disease (AD) and other human tauopathies, a family of neurodegenerative disorders characterized by cognitive and non-cognitive symptoms and with broad differences in neuropathological signs and clinical manifestations, see alterations in the metabolism of tau protein via accumulation in aggregates. The phenotypic heterogeneity of tauopathies represents a challenge in understanding the key pathophysiological mechanisms and in developing diagnostic and therapeutic strategies to slow down disease progression. In order to advance our understanding of tau’s pathogenic role, this Special Issue of the International Journal of Molecular Sciences (IJMS) in the Molecular Neurobiology section is dedicated to publishing research and review articles that provide important findings related to tau-mediated molecular mechanisms of neuronal toxicity and innovative therapies to address these issues.

Dr. Valentina Latina
Dr. Giuseppina Amadoro
Guest Editors

Manuscript Submission Information

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Keywords

  • Alzheimer’s disease
  • tauopathies
  • tau neurotoxicity
  • cellular and animal models
  • signaling pathways
  • tau-targeting therapies
 

Published Papers (1 paper)

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Review

30 pages, 3936 KiB  
Review
The Enigma of Tau Protein Aggregation: Mechanistic Insights and Future Challenges
by Huiting Zheng, Huimin Sun, Qixu Cai and Hwan-Ching Tai
Int. J. Mol. Sci. 2024, 25(9), 4969; https://doi.org/10.3390/ijms25094969 - 2 May 2024
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Abstract
Tau protein misfolding and aggregation are pathological hallmarks of Alzheimer’s disease and over twenty neurodegenerative disorders. However, the molecular mechanisms of tau aggregation in vivo remain incompletely understood. There are two types of tau aggregates in the brain: soluble aggregates (oligomers and protofibrils) [...] Read more.
Tau protein misfolding and aggregation are pathological hallmarks of Alzheimer’s disease and over twenty neurodegenerative disorders. However, the molecular mechanisms of tau aggregation in vivo remain incompletely understood. There are two types of tau aggregates in the brain: soluble aggregates (oligomers and protofibrils) and insoluble filaments (fibrils). Compared to filamentous aggregates, soluble aggregates are more toxic and exhibit prion-like transmission, providing seeds for templated misfolding. Curiously, in its native state, tau is a highly soluble, heat-stable protein that does not form fibrils by itself, not even when hyperphosphorylated. In vitro studies have found that negatively charged molecules such as heparin, RNA, or arachidonic acid are generally required to induce tau aggregation. Two recent breakthroughs have provided new insights into tau aggregation mechanisms. First, as an intrinsically disordered protein, tau is found to undergo liquid-liquid phase separation (LLPS) both in vitro and inside cells. Second, cryo-electron microscopy has revealed diverse fibrillar tau conformations associated with different neurodegenerative disorders. Nonetheless, only the fibrillar core is structurally resolved, and the remainder of the protein appears as a “fuzzy coat”. From this review, it appears that further studies are required (1) to clarify the role of LLPS in tau aggregation; (2) to unveil the structural features of soluble tau aggregates; (3) to understand the involvement of fuzzy coat regions in oligomer and fibril formation. Full article
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