Inhibition of Tau amyloid fibril formation by folic acid: In-vitro and theoretical studies

Ghasemzadeh, Samin; Riazi, Gholam Hossein

doi:10.1016/j.ijbiomac.2019.11.032

Cited by 25 publications

(19 citation statements)

References 82 publications

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“…Samples were protected from light and were gently mixed at 180 rpm for 72 h at 37 °C. The aggregation rate of samples was measured using Thioflavin T assay [ 23 ].…”

Section: Methodsmentioning

confidence: 99%

Cannabidiol Inhibits Tau Aggregation In Vitro

Alali

Riazi

Ashrafi-Kooshk

et al. 2021

Cells

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A hallmark of Alzheimer’s disease (AD) is the accumulation of tau protein in the brain. Compelling evidence indicates that the presence of tau aggregates causes irreversible neuronal destruction, eventually leading to synaptic loss. So far, the inhibition of tau aggregation has been recognized as one of the most effective therapeutic strategies. Cannabidiol (CBD), a major component found in Cannabis sativa L., has antioxidant activities as well as numerous neuroprotective features. Therefore, we hypothesize that CBD may serve as a potent substance to hamper tau aggregation in AD. In this study, we aim to investigate the CBD effect on the aggregation of recombinant human tau protein 1N/4R isoform using biochemical methods in vitro and in silico. Using Thioflavin T (ThT) assay, circular dichroism (CD), atomic force microscopy (AFM), we demonstrated that CBD can suppress tau fibrils formation. Moreover, by quenching assay, docking and job’s plot, we further demonstrate that one molecule of CBD interacts with one molecule of tau protein through a spontaneous binding. Experiments performed by quenching assay, docking and Thioflavin T assay further established that the main forces are hydrogenvan der Waals and some non-negligible hydrophobic forces, affecting the lag phase of tau protein kinetics. Taken together, this study provides new insights about a natural substance, CBD, for tau therapy which may offer new hope for the treatment of AD.

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“…Samples were protected from light and were gently mixed at 180 rpm for 72 h at 37 °C. The aggregation rate of samples was measured using Thioflavin T assay [ 23 ].…”

Section: Methodsmentioning

confidence: 99%

Cannabidiol Inhibits Tau Aggregation In Vitro

Alali

Riazi

Ashrafi-Kooshk

et al. 2021

Cells

View full text Add to dashboard Cite

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“…Another in vitro study has revealed that α-cyperone from rhizomes of Cyperus rotundus (Cyperaceae) exerts a significant effect on reducing the rate of tubulin polymerization and the concentration of polymerized tubulin, which may represent a beneficial neuroprotective strategy for AD [ 155 ]. Other well-known examples of natural products capable of inhibiting tau protein aggregation are curcumin, which inhibits amyloidogenic protein aggregation including Aβ and tau [ 156 ], resveratrol, which inhibits the aggregation of the repeat domain of tau along with many other neuroprotective mechanisms [ 157 ], purpurin, which inhibits tau fibrillization and breaks down the pre-formed fibrils [ 158 ], folic acid, which inhibits tau aggregation via stabilizing its native state [ 159 ], and the root extract of red ginseng [ 160 ].…”

Section: Neuroprotective Mechanisms Of Natural Products For Admentioning

confidence: 99%

Neuroprotective Natural Products for Alzheimer’s Disease

Chen

Drew

Berney

et al. 2021

Cells

137

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Alzheimer’s disease (AD) is the number one neurovegetative disease, but its treatment options are relatively few and ineffective. In efforts to discover new strategies for AD therapy, natural products have aroused interest in the research community and in the pharmaceutical industry for their neuroprotective activity, targeting different pathological mechanisms associated with AD. A wide variety of natural products from different origins have been evaluated preclinically and clinically for their neuroprotective mechanisms in preventing and attenuating the multifactorial pathologies of AD. This review mainly focuses on the possible neuroprotective mechanisms from natural products that may be beneficial in AD treatment and the natural product mixtures or extracts from different sources that have demonstrated neuroprotective activity in preclinical and/or clinical studies. It is believed that natural product mixtures or extracts containing multiple bioactive compounds that can work additively or synergistically to exhibit multiple neuroprotective mechanisms might be an effective approach in AD drug discovery.

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“…Administration of folic acid (1.25 mg/day) improved cognitive scores for patients with AD treated with donepezil in a randomized trial (Chen et al, 2016), indicating that the supplementation may be clinically beneficial. An in vitro study showed that folic acid inhibited tau aggregation by stabilizing the tau native state (Ghasemzadeh and Riazi, 2020). Further, in cultured cells, folic acid reduced the tau phosphorylation level by regulating PP2A methylation (Li et al, 2015).…”

Section: Folic Acidmentioning

confidence: 99%

New Insights Into Drug Discovery Targeting Tau Protein

Soeda

Takashima

2020

Front. Mol. Neurosci.

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Microtubule-associated protein tau is characterized by the fact that it is an intrinsically disordered protein due to its lack of a stable conformation and high flexibility. Intracellular inclusions of fibrillar forms of tau with a β-sheet structure accumulate in the brain of patients with Alzheimer's disease and other tauopathies. Accordingly, detachment of tau from microtubules and transition of tau from a disordered state to an abnormally aggregated state are essential events preceding the onset of tau-related diseases. Many reports have shown that this transition is caused by post-translational modifications, including hyperphosphorylation and acetylation. The misfolded tau is self-assembled and forms a tau oligomer before the appearance of tau inclusions. Animal and pathological studies using human samples have demonstrated that tau oligomer formation contributes to neuronal loss. During the progression of tauopathies, tau seeds are released from cells and incorporated into other cells, leading to the propagation of pathological tau aggregation. Accumulating evidence suggests several potential approaches for blocking tau-mediated toxicity: (1) direct inhibition of pathological tau aggregation and (2) inhibition of tau post-translational modifications that occur prior to pathological tau aggregation, (3) inhibition of tau propagation and (4) stabilization of microtubules. In addition to traditional low-molecular-weight compounds, newer drug discovery approaches such as the development of medium-molecular-weight drugs (peptide- or oligonucleotide-based drugs) and high-molecular-weight drugs (antibody-based drugs) provide alternative pathways to preventing the formation of abnormal tau. Of particular interest are recent studies suggesting that tau droplet formation by liquid-liquid phase separation may be the initial step in aberrant tau aggregation, as well results that implicate roles for tau in dendritic and nuclear functions. Here, we review the mechanisms through which drugs can target tau and consider recent clinical trials for the treatment of tauopathies. In addition, we discuss the utility of these newer strategies and propose future directions for research on tau-targeted therapeutics.

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Inhibition of Tau amyloid fibril formation by folic acid: In-vitro and theoretical studies

Cited by 25 publications

References 82 publications

Cannabidiol Inhibits Tau Aggregation In Vitro

Cannabidiol Inhibits Tau Aggregation In Vitro

Neuroprotective Natural Products for Alzheimer’s Disease

New Insights Into Drug Discovery Targeting Tau Protein

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