Interaction Of Filaments Research Articles

Intrafusal cross-bridge dynamics shape history-dependent muscle spindle responses to stretch.

Computational models can be critical to linking complex properties of muscle spindle organs to the sensory information that they encode during behaviours such as postural sway and locomotion where few muscle spindle recordings exist. Here, we augment a biophysical muscle spindle model to predict the muscle spindle sensory signal. Muscle spindles comprise several intrafusal muscle fibres with varied myosin expression and are innervated by sensory neurons that fire during muscle stretch. We demonstrate how cross-bridge dynamics from thick and thin filament interactions affect the sensory receptor potential at the spike initiating region. Equivalent to the Ia afferent's instantaneous firing rate, the receptor potential is modelled as a linear sum of the force and rate change of force (yank) of a dynamic bag1 fibre and the force of a static bag2/chain fibre. We show the importance of inter-filament interactions in (i) generating large changes in force at stretch onset that drive initial bursts and (ii) faster recovery of bag fibre force and receptor potential following a shortening. We show how myosin attachment and detachment rates qualitatively alter the receptor potential. Finally, we show the effect of faster recovery of receptor potential on cyclic stretch-shorten cycles. Specifically, the model predicts history-dependence in muscle spindle receptor potentials as a function of inter-stretch interval (ISI), pre-stretch amplitude and the amplitude of sinusoidal stretches. This model provides a computational platform for predicting muscle spindle response in behaviourally relevant stretches and can link myosin expression seen in healthy and diseased intrafusal muscle fibres to muscle spindle function.

A Preliminary Observation Study to Evaluate Safety and Efficacy of Boheco Ease in Myalgia

One of the most frequent concerns at emergency departments and clinics across the nation is muscle soreness and fatigue. Oftentimes, severe pain and fatigue subside on their own or seem to do so in response to several medications and therapeutic methods. Excitation-contraction coupling in the muscle, and actin-myosin filament interactions, decreased function can lead to failure of voluntary muscle contraction. The two most powerful Phyto-cannabinoids found in the Cannabis sativa plant are CBD (cannabidiol) and delta-9-tetrahydrocannabinol (THC). CBD was effectively delivered trans dermally for anti-inflammatory activity in various animals. Cannabis sativa or Vijaya has Shulahara property as per Ayurveda. Muscle pain and Swelling are caused by a rise in the Ruksha and Sheeta qualities of the Vata dosha and accumulation of Kleda. Cannabis sativa, also known as Vijaya, has Ushna properties that have the power to reduce Vata dosha. It has Pachak property which helps to mitigate Kleda. Oil tends to decrease Rukshata due to Vata dosha. As a result, reducing pain and inflammation which also lessens discomfort and irritation. Methods: A preliminary survey on 30 patients was conducted and data was collected. Results: More than 90% of patients had reduced symptoms of pain and inflammation in muscles, post-application twice a day with a lasting effect of more than 3 hours. It helps in reducing Kleda present in muscles. Conclusions: Ease oil was having a better result in patients having myalgia. It was safe on use for long term.

Dietary fiber and Segmented Filamentous Bacteria interaction with intestinal epithelial cells supports the development of CD4 +CD8αα +intraepithelial T cells

Abstract Double positive intraepithelial lymphocytes (DP IELs) are microbiome induced CD4 +CD8αα +T cells that play a role in maintaining homeostasis and reducing inflammation in the small intestine. While the impact of the microbiome on the intestinal immune system has been extensively studied, little is known about how changes in macronutrients, such as dietary fiber, affect the development of important immune cell populations through changes in the microbiome. Here we show that a diet low in fermentable fiber (LFF) impairs development of DP IELs by reducing MHC-II expression on intestinal epithelial cells (IECs). Bulk RNA sequencing of ileal IECs revealed that LFF fed mice had lower expression of genes associated with the antigen presentation machinery. Subsequently, flow cytometry analysis confirmed increased expression of MHC-II on IECs in standard chow fed mice, which is required for DP IEL development. 16s rRNA sequencing of the microbiota of LFF mice showed that SFB is reduced in these animals. We found that colonizing mice with SFB induces MHC-II expression on IECs and restores development of DP IELs in a fiber-dependent manner. Finally, using the offspring of mice that naturally harbor SFB, we show that MHC-II expression on IECs and IFN-γ levels in the ileum increase gradually over time and correlate with SFB colonization. These results suggest that dietary fiber is required for the development of DP IELs through supporting SFB colonization and increasing expression of MHC-II on small intestinal epithelial cells. Supported by grants from NIH (1R011DK129950) and startup funds from Emory University

Drag reduction by flapping a pair of flexible filaments behind a cylinder

The hydrodynamic mechanism of drag reduction by flapping a pair of flexible filaments behind a cylinder was explored using the penalty immersed boundary method. The effects of the phase difference between two filaments, the attachment height, and the flapping amplitude on drag reduction were examined. The flapping filaments weaken the vortex shedding via the destructive interaction between the vortices with the opposite signal. The clapping (out-of-phase) flexible filaments experience a lower friction drag and reduce a form drag of the cylinder, showing a better drag reduction than the snaking (in-phase) flexible filaments and the clapping rigid filaments. A minimum drag is obtained at an appropriate attachment height and flapping amplitude that avoid collision of the filaments and weaken the shear-layer–filaments interaction. The effectiveness ratio of the clapping filaments is higher than that of the snaking filaments. Energy saving can be achieved by avoiding the shear layer–filament interaction at a low flapping amplitude, whereas the filaments can further reduce the drag with greater energy consumption at an appropriate flapping amplitude. In addition, the total drag decreases with increasing Reynolds number, accompanied by a transition of the wake pattern from the 2S mode to the P + S mode.

Ammonia mapping observations of the Galactic infrared bubble N49: Three NH3 clumps along the molecular filament

Abstract We have carried out the NH3(J, K) = (1, 1), (2, 2), and (3, 3) mapping observations toward the Galactic infrared bubble N49 (G28.83−0.25) using the Nobeyama 45 m telescope. Three NH3 clumps (A, B, and C) were discovered along the molecular filament with the radial velocities of ∼96, 87, and 89 km s−1, respectively. The kinetic temperature derived from the NH3(2, 2)/NH3(1, 1) shows Tkin = 27.0 ± 0.6 K enhanced at Clump B in the eastern edge of the bubble, where position coincides with massive young stellar objects (MYSOs) associated with the 6.7 GHz class II methanol maser source. This result shows the dense clump is locally heated by stellar feedback from the embedded MYSOs. The NH3 Clump B also exists at the 88 km s−1 and 95 km s−1 molecular filament intersection. We therefore suggest that the NH3 dense gas formation in Clump B can be explained by a filament–filament interaction scenario. On the other hand, NH3 Clumps A and C at the northern and southern sides of the molecular filament might be the sites of spontaneous star formation because these clumps are located ∼ 5–10 pc away from the edge of the bubble.

Advances in Understanding the Molecular Mechanisms of Neuronal Polarity.

The establishment and maintenance of neuronal polarity are important for neural development and function. Abnormal neuronal polarity establishment commonly leads to a variety of neurodevelopmental disorders. Over the past three decades, with the continuous development and improvement of biological research methods and techniques, we have made tremendous progress in the understanding of the molecular mechanisms of neuronal polarity establishment. The activity of positive and negative feedback signals and actin waves are both essential in this process. They drive the directional transport and aggregation of key molecules of neuronal polarity, promote the spatiotemporalregulationof ordered and coordinated interactions of actin filaments and microtubules, stimulate the specialization and growth of axons, and inhibit the formation of multiple axons. In this review, we focus on recent advances in these areas, in particular the important findings about neuronal polarity in two classical models, in vitro primary hippocampal/cortical neurons and in vivo cortical pyramidal neurons, and discuss our current understanding of neuronal polarity.​.

Towards cell scale agent-based models for membrane cytoskeleton interactions.

The cytoskeleton is a dynamic far-from-equilibrium polymer network. It consumes energy to do mechanical work, and it interacts with complex chemical reaction networks in the cytoplasm and cell membrane to organize into various structures. We will discuss how the MEDYAN (medyan.org) model and software can simulate the chemical and mechanical interactions of actin filaments, crosslinks, myosin motor proteins, and membranes at the micrometer length scale and minute time scale. The next generation of MEDYAN is written in the Julia programming language (MEDYAN.jl). It has significant performance improvements including a 10x faster cylinder volume exclusion algorithm and a 10x faster Gillespie implementation for scheduling chemical reaction events. In addition, it includes an HDF5-based snapshot format that stores the full state of the simulation and enables restarts, and detailed linker and filament aging reactions that have reaction rates that adjust to changes to local monomer states, linker states, and linker mechanics. More complex reactions and reaction rates can be added using user-defined reaction callbacks. It also includes a deformable mesh-based membrane model. MEDYAN.jl is being used to study the role of ARP2/3 in the actin structure in the core of an axon growth cone. MEDYAN.jl is also being used to prototype models of membrane cytoskeleton chemical and mechanical interactions, including activation of ARP2/3.

Galaxy Interactions in Filaments and Sheets: Effects of the Large-scale Structures Versus the Local Density

Major interactions are known to trigger star formation in galaxies and alter their color. We study the major interactions in filaments and sheets using SDSS data to understand the influence of large-scale environments on galaxy interactions. We identify the galaxies in filaments and sheets using the local dimension and also find the major pairs residing in these environments. The star formation rate (SFR) and color of the interacting galaxies as a function of pair separation are separately analyzed in filaments and sheets. The analysis is repeated for three volume limited samples covering different magnitude ranges. The major pairs residing in the filaments show a significantly higher SFR and bluer color than those residing in the sheets up to the projected pair separation of ∼50 kpc. We observe a complete reversal of this behavior for both the SFR and color of the galaxy pairs having a projected separation larger than 50 kpc. Some earlier studies report that the galaxy pairs align with the filament axis. Such alignment inside filaments indicates anisotropic accretion that may cause these differences. We do not observe these trends in the brighter galaxy samples. The pairs in filaments and sheets from the brighter galaxy samples trace relatively denser regions in these environments. The absence of these trends in the brighter samples may be explained by the dominant effect of the local density over the effects of the large-scale environment.

Targeted transcript analysis in muscles from patients with genetically diverse congenital myopathies.

Congenital myopathies are a group of early onset muscle diseases of variable severity often with characteristic muscle biopsy findings and involvement of specific muscle types. The clinical diagnosis of patients typically relies on histopathological findings and is confirmed by genetic analysis. The most commonly mutated genes encode proteins involved in skeletal muscle excitation–contraction coupling, calcium regulation, sarcomeric proteins and thin–thick filament interaction. However, mutations in genes encoding proteins involved in other physiological functions (for example mutations in SELENON and MTM1, which encode for ubiquitously expressed proteins of low tissue specificity) have also been identified. This intriguing observation indicates that the presence of a genetic mutation impacts the expression of other genes whose product is important for skeletal muscle function. The aim of the present investigation was to verify if there are common changes in transcript and microRNA expression in muscles from patients with genetically heterogeneous congenital myopathies, focusing on genes encoding proteins involved in excitation–contraction coupling and calcium homeostasis, sarcomeric proteins, transcription factors and epigenetic enzymes. Our results identify RYR1, ATPB2B and miRNA-22 as common transcripts whose expression is decreased in muscles from congenital myopathy patients. The resulting protein deficiency may contribute to the muscle weakness observed in these patients. This study also provides information regarding potential biomarkers for monitoring disease progression and response to pharmacological treatments in patients with congenital myopathies.

Experimental study on counter-propagating filaments in air

We experimentally investigate the interaction of two collinearly counter-propagating filaments in air. The fluorescence is enhanced by 4 times due to the increase of the clamped intensity and electron (or plasma) density. The output energy at the end of a filament, the spectra of the excitation beams, and the fluorescent intensity are found to be dependent on the relative pulse delays between the counter-propagating pulses. The results indicate that the modulation of the filamentation-induced fluorescence intensity with another filament launched from the opposite direction is feasible, which provides a new perspective for studying the interaction of filaments and may improve the detection sensitivity for fluorescence sensing.

Characterization of Electromagnetic Pulses Generated from Plasma Associated with Laser Filaments-Excited Aluminum Alloy Interaction

Femtosecond laser filament-generated plasma can generate electromagnetic pulses (EMPs). These pulses may reduce the instrument’s precision, and, hence, influence the accuracy of the experimental results. They may even cause widespread disruption by disabling of the electronic control systems or distribution networks of power plants. This study investigated the characteristics of EMPs generated from the interaction of filament-generated plasmas with a solid target in air. In this study, ultrafast laser filamentation was used to produce plasma, which was focused on a 3 mm-thick aluminum (Al) alloy target for interaction, and the spatial distribution and main contributors of the EMPs were systematically and extensively studied. The results showed that the EMPs generated from ultrafast laser filament interaction with the Al alloy target had the following characteristics: the EMP energy generated from laser filament interaction with solid targets is tens of times higher than that generated only from the femtosecond laser filament; the maximum EMP signals appeared at a 20°–80°detection angle. The relationship between the energy of EMPs and the width and energy of the laser pulses is presented and discussed. These findings are beneficial for gaining insight into the EMP generation mechanism, spatial distribution, and transmission, and for providing more information for the design of EMPs’ shielding.

The NuSTAR, XMM-Newton, and Suzaku View of A3395 at the Intercluster Filament Interface

Galaxy clusters are the largest virialized objects in the universe. Their merger dynamics and their interactions with the cosmic filaments that connect them are important for our understanding of the formation of large-scale structure. In addition, cosmic filaments are thought to possess the missing baryons in the universe. Studying the interaction of galaxy clusters and filaments therefore has the potential to unveil the origin of the baryons and the physical processes that occur during merger stages of galaxy clusters. In this paper, we study the connection between A3395 and the intercluster filament with NuSTAR, XMM-Newton, and Suzaku data. Since the NuSTAR observation is moderately contaminated by scattered light, we present a novel technique developed for disentangling this background from the emission from the intracluster medium. We find that the interface of the cluster and the intercluster filament connecting A3395 and A3391 does not show any signs of heated plasma, as was previously thought. This interface has low temperature, high density, and low entropy, thus we suggest that the gas is cooling, being enhanced by the turbulent or tidal “weather” driven during the early stage of the merger. Furthermore, our temperature results from the NuSTAR data are in agreement with those from XMM-Newton and from joint NuSTAR and XMM-Newton analysis for a region with ∼25% scattered light contamination within 1σ. We show that the temperature constraint of the intracluster medium is valid even when the data are contaminated up to ∼25% for ∼5 keV cluster emission.

Gibbs spatial process for characterization of filament interaction in ReRAM devices via photon emission microscopy

In this work, we investigate spatial statistical properties of filament patterns in resistive random-access memory (ReRAM) devices measured from a newly developed near-infrared photon emission microscopy (PEM) [Stellari et al., IEEE Electron Device Lett. 42, 828 (2021); Stellari et al., in Proceedings of the 47th International Symposium for Testing and Failure Analysis Conference (ISTFA) (ASM International, 2021), pp. 115–121]. Unlike previous reports on uncorrelated filaments [Stellari et al., IEEE Electron Device Lett. 42, 828 (2021); Wu et al., Appl. Phys. Lett. 99, 093502 (2011)], we report a strong clustering and non-Poisson pattern of filaments constructed from individual devices. A Poisson-mixture model incorporating the clustering (attractive) effect is introduced with an excellent agreement with the PEM data for global and nearest-neighbor spatial statistics. On the other hand, a two-filament pattern is also detected within the ReRAM devices. We found that both attractive and repulsive interactions among the filaments are required in a Gibbs process to explain the filament spatial distribution. We implemented a birth-death algorithm using a Markov-chain Monte Carlo approach and achieve good agreement with the PEM data using a generalized Morse potential.

Frameshift mutation S368fs in the gene encoding cytoskeletal β-actin leads to ACTB-associated syndromic thrombocytopenia by impairing actin dynamics

Heterozygous dominant mutations in the ubiquitously produced cytoskeletal β–actin isoform lead to a broad range of human disease phenotypes, which are currently classified as three distinct clinical entities termed Baraitser-Winter–Cerebrofrontofacial syndrome (BWCFF), ACTB–associated pleiotropic malformation syndrome with intellectual disability (ACTB–PMSID), and ACTB–associated syndromic thrombocytopenia (ACTB–AST). The latter two are distinguishable from BWCFF by the presence of milder craniofacial features and less pronounced developmental abnormalities, or the absence of craniofacial features in combination with a characteristic thrombocytopenia with platelet anisotropy. Production and correct function of β–actin is required for multiple essential processes in all types of cells. Directed cell migration, cytokinesis and morphogenesis are amongst the functions that are supported by β–actin. Here we report the recombinant production and biochemical characterization of the ACTB–AST mutant p.S368fs, resulting in an altered sequence in the C–terminal region of β–actin that includes a replacement of the last 8 residues and an elongation of the molecule by 4 residues. The mutation affects a region important for actin polymerization and actin–profilin interaction. Accordingly, we measured markedly reduced rates of nucleation and polymerization during spontaneous actin assembly and lower affinity of p.S368fs for human profilin–1. The reduced affinity is also reflected in the lower propensity of profilin–1 to extend the nucleation phase of p.S368fs. While localized in close proximity to actin–cofilin and actin–myosin interfaces, we determined only minor effects of the mutation on the interaction of mutant filaments with cofilin and myosin family members. However, allosteric effects on sites distant from the mutation manifest themselves in a 7.9 °C reduction in thermal denaturation temperature, a 2–fold increase in the observed IC50 for DNase–I, and changes in nucleotide exchange kinetics. Our results support a disease mechanism involving impaired actin dynamics and function through disruption of actin–profilin interactions and further exacerbated by allosteric perturbations.

Resonant wave–filament interactions as a loss mechanism for HHFW heating and current drive

Perkins et al (2012 Phys. Rev. Lett. 109 045001) reported unexpected power losses during high harmonic fast wave (HHFW) heating and current drive in the National Spherical Torus Experiment (NSTX). Recently, Tierens et al (2020 Phys. Plasmas 27 010702) proposed that these losses may be attributable to surface waves on field-aligned plasma filaments, which carry power along the filaments, to be lost at the endpoints where the filaments intersect the limiters. In this work, we show that there is indeed a resonant loss mechanism associated with the excitation of these surface waves, and derive an analytic expression for the power lost to surface wave modes at each filament.

Modeling rigid filament interaction under oscillatory flow using immersed boundary method

The thread-like biological filament structures can enhance many processes such as fluid transport, locomotion, defence against foreign bodies etc. Researchers have tried to mimic these filament movements to improve fluid transport, mixing, drug delivery for microfluidic applications. These biological filaments can be modelled as slender rigid filaments which can be either active or passive. Active filaments move on their own thus causing a disruption in the fluid domain in close vicinity while passive filaments undergo motion depending upon the fluid flow past them. The dynamics of both active and passive filaments in low Reynolds number flow has immense research potential. In the case of passive filament, the nature of the incoming flow field is an important factor that affects the flow physics around the filament. This paper studies the flow dynamics of vertical and inclined passive rigid filaments in an oscillatory flow. The effect of change in flow conditions is studied by varying the Reynolds and Strouhal numbers. The simulation involves fluid-structure interaction which is implemented with the help of continuous forcing based immersed boundary (IB) method using finite volume discretization. This is a preliminary work towards modelling active filaments under different fluid flow conditions in channel in the near future.

The effects of the tropomyosin cardiomyopathy mutations on the calcium regulation of actin-myosin interaction in the atrium and ventricle differ

The molecular mechanisms of pathogenesis of atrial myopathy associated with hypertrophic (HCM) and dilated (DCM) mutations of sarcomeric proteins are still poorly understood. For this, one needs to investigate the effects of the mutations on actin-myosin interaction in the atria separately from ventricles. We compared the impact of the HCM and DCM mutations of tropomyosin (Tpm) on the calcium regulation of the thin filament interaction with atrial and ventricular myosin using an in vitro motility assay. We found that the mutations differently affect the calcium regulation of actin-myosin interaction in the atria and ventricles. The DCM E40K Tpm mutation significantly reduced the maximum sliding velocity of thin filaments with ventricular myosin and its Ca2+-sensitivity. With atrial myosin, its effects were less pronounced. The HCM I172T mutation reduced the Ca2+-sensitivity of the sliding velocity of filaments with ventricular myosin but increased it with the atrial one. The HCM L185R mutation did not affect actin-myosin interaction in the atria. The results indicate that the difference in the effects of Tpm mutations on the actin-myosin interaction in the atria and ventricles may be responsible for the difference in pathological changes in the atrial and ventricular myocardium.

Structural basis of the super- and hyper-relaxed states of myosin II.

Super-relaxation is a state of muscle thick filaments in which ATP turnover by myosin is much slower than that of myosin II in solution. This inhibited state, in equilibrium with a faster (relaxed) state, is ubiquitous and thought to be fundamental to muscle function, acting as a mechanism for switching off energy-consuming myosin motors when they are not being used. The structural basis of super-relaxation is usually taken to be a motif formed by myosin in which the two heads interact with each other and with the proximal tail forming an interacting-heads motif, which switches the heads off. However, recent studies show that even isolated myosin heads can exhibit this slow rate. Here, we review the role of head interactions in creating the super-relaxed state and show how increased numbers of interactions in thick filaments underlie the high levels of super-relaxation found in intact muscle. We suggest how a third, even more inhibited, state of myosin (a hyper-relaxed state) seen in certain species results from additional interactions involving the heads. We speculate on the relationship between animal lifestyle and level of super-relaxation in different species and on the mechanism of formation of the super-relaxed state. We also review how super-relaxed thick filaments are activated and how the super-relaxed state is modulated in healthy and diseased muscles.

Resistance of Acta2R149C/+ mice to aortic disease is associated with defective release of mutant smooth muscle α-actin from the chaperonin-containing TCP1 folding complex

Pathogenic variants of the gene for smooth muscle α-actin (ACTA2), which encodes smooth muscle (SM) α-actin, predispose to heritable thoracic aortic disease. The ACTA2 variant p.Arg149Cys (R149C) is the most common alteration; however, only 60% of carriers have a dissection or undergo repair of an aneurysm by 70 years of age. A mouse model of ACTA2 p.Arg149Cys was generated using CRISPR/Cas9 technology to determine the etiology of reduced penetrance. Acta2R149C/+ mice had significantly decreased aortic contraction compared with WT mice but did not form aortic aneurysms or dissections when followed to 24 months, even when hypertension was induced. In vitro motility assays found decreased interaction of mutant SM α-actin filaments with SM myosin. Polymerization studies using total internal reflection fluorescence microscopy showed enhanced nucleation of mutant SM α-actin by formin, which correlated with disorganized and reduced SM α-actin filaments in Acta2R149C/+ smooth muscle cells (SMCs). However, the most prominent molecular defect was the increased retention of mutant SM α-actin in the chaperonin-containing t-complex polypeptide folding complex, which was associated with reduced levels of mutant compared with WT SM α-actin in Acta2R149C/+ SMCs. These data indicate that Acta2R149C/+ mice do not develop thoracic aortic disease despite decreased contraction of aortic segments and disrupted SM α-actin filament formation and function in Acta2R149C/+ SMCs. Enhanced binding of mutant SM α-actin to chaperonin-containing t-complex polypeptide decreases the mutant actin versus WT monomer levels in Acta2R149C/+ SMCs, thus minimizing the effect of the mutation on SMC function and potentially preventing aortic disease in the Acta2R149C/+ mice.

Green Tea Polyphenol Epigallocatechin-Gallate in Amyloid Aggregation and Neurodegenerative Diseases.

The accumulation of protein aggregates in human tissues is a hallmark of more than 40 diseases called amyloidoses. In seven of these disorders, the aggregation is associated with neurodegenerative processes in the central nervous system such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD). The aggregation occurs when certain soluble proteins lose their physiological function and become toxic amyloid species. The amyloid assembly consists of protein filament interactions, which can form fibrillar structures rich in β-sheets. Despite the frequent incidence of these diseases among the elderly, the available treatments are limited and at best palliative, and new therapeutic approaches are needed. Among the many natural compounds that have been evaluated for their ability to prevent or delay the amyloidogenic process is epigallocatechin-3-gallate (EGCG), an abundant and potent polyphenolic molecule present in green tea that has extensive biological activity. There is evidence for EGCG’s ability to inhibit the aggregation of α-synuclein, amyloid-β, and huntingtin proteins, respectively associated with PD, AD, and HD. It prevents fibrillogenesis (in vitro and in vivo), reduces amyloid cytotoxicity, and remodels fibrils to form non-toxic amorphous species that lack seed propagation. Although it is an antioxidant, EGCG in an oxidized state can promote fibrils’ remodeling through formation of Schiff bases and crosslinking the fibrils. Moreover, microparticles to drug delivery were synthesized from oxidized EGCG and loaded with a second anti-amyloidogenic molecule, obtaining a synergistic therapeutic effect. Here, we describe several pre-clinical and clinical studies involving EGCG and neurodegenerative diseases and their related mechanisms.