Tau Oligomers Neurotoxicity

Niewiadomska, Grażyna; Niewiadomski, Wiktor; Steczkowska, Marta; Gąsiorowska, Anna

doi:10.3390/life11010028

Cited by 63 publications

(54 citation statements)

References 227 publications

(286 reference statements)

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“…the brain tissue of patients with AD(Grundke-Iqbal et al, 1986;Meraz-Ríos et al, 2010). Recent, comprehensive reviews byNiewiadomska et al (2021) andShafiei et al (2017) have established oligomeric assemblies of tau as cytotoxic species.…”

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confidence: 99%

Arginine and Arginine-Rich Peptides as Modulators of Protein Aggregation and Cytotoxicity Associated With Alzheimer’s Disease

Mamsa

Meloni

2021

Front. Mol. Neurosci.

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A substantial body of evidence indicates cationic, arginine-rich peptides (CARPs) are effective therapeutic compounds for a range of neurodegenerative pathologies, with beneficial effects including the reduction of excitotoxic cell death and mitochondrial dysfunction. CARPs, therefore, represent an emergent class of promising neurotherapeutics with multimodal mechanisms of action. Arginine itself is a known chaotrope, able to prevent misfolding and aggregation of proteins. The putative role of proteopathies in chronic neurodegenerative diseases such as Alzheimer’s disease (AD) warrants investigation into whether CARPs could also prevent the aggregation and cytotoxicity of amyloidogenic proteins, particularly amyloid-beta and tau. While monomeric arginine is well-established as an inhibitor of protein aggregation in solution, no studies have comprehensively discussed the anti-aggregatory properties of arginine and CARPs on proteins associated with neurodegenerative disease. Here, we review the structural, physicochemical, and self-associative properties of arginine and the guanidinium moiety, to explore the mechanisms underlying the modulation of protein aggregation by monomeric and multimeric arginine molecules. Arginine-rich peptide-based inhibitors of amyloid-beta and tau aggregation are discussed, as well as further modulatory roles which could reduce proteopathic cytotoxicity, in the context of therapeutic development for AD.

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confidence: 99%

Arginine and Arginine-Rich Peptides as Modulators of Protein Aggregation and Cytotoxicity Associated With Alzheimer’s Disease

Mamsa

Meloni

2021

Front. Mol. Neurosci.

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“…These factors complicate the rational design of antibodies targeting specific Tau proteoforms due to our limited knowledge of the relevance of these proteoforms to pathological processes, as well as the difficulties to reconstruct the complexity of native Tau proteoforms in vitro for the antibody design and screening. Therefore, the exact species of Tau targeted by antibodies are not well defined, 321 and their formation pathways and clinical relevance remain unknown.…”

Section: How Can the New Biochemical And Structural Insights Into Physiological And Pathogenic Tau Inform Drug Discovery?mentioning

confidence: 99%

Revisiting the grammar of Tau aggregation and pathology formation: how new insights from brain pathology are shaping how we study and target Tauopathies

Limorenko

Lashuel

2022

Chem. Soc. Rev.

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“…Recent experimental evidence has pointed out the importance of extracellular tau oligomers in neurodegeneration, even if the mechanisms by which these aggregates induce cell death are not yet fully understood [ 121 ].…”

Section: Functional Commonalitiesmentioning

confidence: 99%

Amyloid Prefibrillar Oligomers: The Surprising Commonalities in Their Structure and Activity

Diociaiuti

Bonanni

Cariati

et al. 2021

IJMS

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It has been proposed that a “common core” of pathologic pathways exists for the large family of amyloid-associated neurodegenerations, including Alzheimer’s, Parkinson’s, type II diabetes and Creutzfeldt–Jacob’s Disease. Aggregates of the involved proteins, independently from their primary sequence, induced neuron membrane permeabilization able to trigger an abnormal Ca2+ influx leading to synaptotoxicity, resulting in reduced expression of synaptic proteins and impaired synaptic transmission. Emerging evidence is now focusing on low-molecular-weight prefibrillar oligomers (PFOs), which mimic bacterial pore-forming toxins that form well-ordered oligomeric membrane-spanning pores. At the same time, the neuron membrane composition and its chemical microenvironment seem to play a pivotal role. In fact, the brain of AD patients contains increased fractions of anionic lipids able to favor cationic influx. However, up to now the existence of a specific “common structure” of the toxic aggregate, and a “common mechanism” by which it induces neuronal damage, synaptotoxicity and impaired synaptic transmission, is still an open hypothesis. In this review, we gathered information concerning this hypothesis, focusing on the proteins linked to several amyloid diseases. We noted commonalities in their structure and membrane activity, and their ability to induce Ca2+ influx, neurotoxicity, synaptotoxicity and impaired synaptic transmission.

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Tau Oligomers Neurotoxicity

Cited by 63 publications

References 227 publications

Arginine and Arginine-Rich Peptides as Modulators of Protein Aggregation and Cytotoxicity Associated With Alzheimer’s Disease

Arginine and Arginine-Rich Peptides as Modulators of Protein Aggregation and Cytotoxicity Associated With Alzheimer’s Disease

Revisiting the grammar of Tau aggregation and pathology formation: how new insights from brain pathology are shaping how we study and target Tauopathies

Amyloid Prefibrillar Oligomers: The Surprising Commonalities in Their Structure and Activity

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