Trehalose Molecules Research Articles

Mode coupling behavior and fragile to strong transition of trehalose in a binary mixture with water upon supercooling.

We perform molecular dynamics simulations of a binary mixture of water and trehalose with the TIP4P/Ice water model. We analyze the slow dynamics of trehalose molecules in the mildly supercooled region for concentrations of 3.66 and 18.57 wt. %. We previously studied the dynamics of water in the same mixtures. Supercooled TIP4P/Ice water solvating trehalose molecules was found to follow the Mode Coupling Theory (MCT) and to undergo a transition from a fragile to a strong behavior for both concentrations. Here, we show that also the dynamics of trehalose molecules follows the MCT and displays a fragile to strong crossover (FSC). The results show that trehalose in binary mixtures with water shares with it the dynamical behavior typical of glass forming liquids. Moreover, the FSC for trehalose structural relaxation times is found to occur at temperatures close to those previously obtained for water in the same solutions, showing that the dynamics of the solute is strongly coupled to that of the solvent. We also perform a MCT test showing that the trehalose dynamics obeys the MCT time-temperature superposition principle and that the exponents derived from the theory and the ones obtained from fitting procedure of the relaxation times are comparable, confirming that trehalose molecules in supercooled water solutions follow the MCT of glassy dynamics. Moreover, as predicted by the theory, trehalose particles have MCT parameters comparable to those of water in the same mixtures. This is an important result, given that MCT was originally formulated for monoatomic particles.

Investigation of the affinity and interaction of fibrinogen with trehalose as a protein stabilizer

Trehalose, a remarkable substance, holds great importance in biomedicine for its anti-inflammatory properties and its capacity to hinder scar formation at wounds. This study aims to explore how trehalose interacts with fibrinogen, a crucial protein in wound healing, paying particular attention to their structural characteristics. An array of analytical methods, such as steady-state fluorescence, UV–Vis analysis, circular dichroism (CD), Zeta potential measurements, Dynamic light scattering (DLS), and Fourier-transform infrared spectroscopy (FT-IR), are employed to examine the influence of trehalose on fibrinogen. The findings demonstrate that trehalose induces structural alterations on the surface of fibrinogen, resulting in its compaction. Moreover, computational modeling approaches like docking and molecular dynamics simulations are utilized to enhance the understanding of the interactions between trehalose and fibrinogen. The findings indicate the establishment of a stable complex between the two entities, accompanied by slight modifications in the protein's structure due to their interaction. The main forces facilitating the bonding of trehalose (the ligand) and the protein are hydrogen bonds and van der Waals forces, resulting in an entropy-driven spontaneous bonding process. FT-IR data reveals the emergence of fresh bonds between fibrinogen and trehalose post their interaction, whereas Zeta potential investigations suggest that the engagement with trehalose enhances the stability of the protein structure.Tests assessing cytotoxicity on a typical fibroblast cell line demonstrated that the fibrinogen-trehalose compound displays lower toxicity levels compared to trehalose alone. This suggests a milder impact on cells from the compound. Moreover, molecular docking analysis supports these experimental results, indicating that trehalose molecules primarily bind to the C-terminal end of the coiled-coil segment and the globular area of the Bβ chain within the Dβ fragment. These outcomes highlight the promise of trehalose as a valuable material for wound dressing purposes.

Noncovalent cross-linked engineering hydrogel with low hysteresis and high sensitivity for flexible self-powered electronics

In this study, the hydrogel network was reinforced by covalent-like hydrogen bonding, and the strong binding ability of boron–nitrogen coordination served as the main driving force. Among them, acrylamide (AM) and 3-acrylamidophenylboronic acid (AAPBA) were the main body, and the numerous hydroxyl groups in the trehalose (Treh) molecule and other polymer groups formed strong hydrogen bonding interactions to improve the mechanical properties of the PAM/PAAPBA/Treh (PAAT) hydrogel and ensured the simplicity of the synthesis process. The hydrogel possessed high strain at break (1239%), stress (64.7 kPa), low hysteresis (100% to 500% strain, corresponding to dissipation energy from 1.37 to 7.80 kJ/m3), and outstanding cycling stability (retained more than 90% of maximum stress after 200 tensile cycles). By integrating carbon nanotubes (CNTs) into PAAT hydrogel (PAATC), the PAATC hydrogel with excellent strain response performance was successfully constructed. The PAATC conductive hydrogel exhibited high sensitivity (gauge factor (GF) = 10.58 and sensitivity (S) = 0.304 kPa−1), wide strain response range (0.5%–1000%), fast response time (450 ms), and short recovery time (350 ms), excellent fatigue resistance, and strain response stability. Furthermore, the PAATC-based triboelectric nanogenerator (TENG) displayed outstanding energy harvesting performance, which shows its potential for application in self-powered electronic devices.

The effects of dextran in residual impurity on trehalose crystallization and formula in food preservation

The residual dextran impurities in the upstream process significantly impact the crystallization of starch-based functional sugar and the related food properties. This study intends to reveal the mechanism of dextran’s influence on trehalose crystallization, and build a relationship among the dextran in syrup and the physicochemical and functional properties of trehalose. Instead of incorporating into the crystal lattice, dextran changes the assembly rate of trehalose molecules on crystal surface. The different sensitivity and adsorption capacity of the crystal surface to the chain length of dextran determines the growth rate of crystal surfaces, resulting in different crystal morphology. The bulk trehalose crystals, which were obtained from syrups with short chain dextran, have excellent powder properties, including best flowability (35◦), highest crystal strength (2.7 N), lowest caking rate (62.22 %), and the most uniform mixing with other sweeteners (sucrose/xylitol) in food formulations, achieving more stable starch preservation.

Glassy dynamics of water in TIP4P/Ice aqueous solutions of trehalose in comparison with the bulk phase.

We perform molecular dynamics simulations of TIP4P/Ice water in solution with trehalose for 3.65 and 18.57 wt. % concentrations and of bulk TIP4P/Ice water at ambient pressure, to characterize the structure and dynamics of water in a sugar aqueous solution in the supercooled region. We find here that TIP4P/Ice water in solution with trehalose molecules follows the Mode Coupling Theory and undergoes a fragile to strong transition up to the highest concentration investigated, similar to the bulk. Moreover, we perform a Mode Coupling Theory test, showing that the Time Temperature Superposition principle holds for both bulk TIP4P/Ice water and for TIP4P/Ice water in the solutions and we calculate the exponents of the theory. The direct comparison of the dynamical results for bulk water and water in the solutions shows upon cooling along the isobar a fastening of water dynamics for lower temperatures, T < 240K. We found that the counter-intuitive behavior for the low temperature solutions can be explained with the diffusion anomaly of water leading us to the conclusion that the fastening observed below T = 240K in water dynamics is only fictitious, due to the fact that the density of water molecules in the solutions is higher than the density of the bulk at the same temperature and pressure. This result should be taken into account in experimental investigations which are often carried out at constant pressure.

Dehydrogenation versus deprotonation of disaccharide molecules in vacuum: a thorough theoretical investigation.

Dehydrogenation and deprotonation of sucrose and trehalose molecules in vacuum is theoretically studied by using ab initio calculations in the framework of the density functional theory. The differences in the structural, electronic, energetic and vibrational properties of dehydrogenated and deprotonated molecules are discussed, depending on the site from which the hydrogen atom or the proton has been removed. The dehydrogenated molecules are found to be stable, regardless of which hydrogen atom is removed. This contrasts with the instability of the deprotonated molecules, where break-ups or structural reorganizations of the molecule are observed in 20–30% of the cases, but only when the hydrogen atom whose proton is removed was bonded to a carbon atom. Considering the stability and possible rearrangements of the hydrogen network of the deprotonated/dehydrogenated molecule, the formation of additional hydrogen-bridge bonds compared with the nominal molecule appears to be more pronounced for the deprotonated molecules than for the dehydrogenated ones. Moreover, our calculations show that the hydrogen-transfer energy barriers are usually larger for the deprotonated molecules than for the dehydrogenated ones. Finally, compared with the nominal molecule, the vibrational frequency spectrum is shifted to lower frequencies for both the dehydrogenated and the deprotonated molecules.

Priming with fungal elicitor elicits early signaling defense against leaf spot of broccoli underlying cellular, biochemical and gene expression

The phytopathogen Alternaria, which causes leaf spot disease in broccoli plants, has developed the ability to adapt to changing climatic conditions with the failure of conventional fungicides. To restrict its infection and further spread, the application of novel molecules that have the ability to trigger innate immune responses of the plants to concurrent pathogenic invasions is essential. In this context, the current study was set out to assess Trichoderma-derived trehalose molecules' beneficial effects from inciting resistance mechanisms in broccoli plants against Alternaria brassicicola at histochemical, biochemical and genetic levels. From the results of the greenhouse experiment, it was evident that trehalose proved to be an exceptional elicitor in combating broccoli leaf spot disease. The induced resistance is positively associated with an early hypersensitive reaction expressed in the primed seedlings. Additionally, the deposition of histochemical such as callose and phenols was found to be accelerated in the tripartite system at 24 and 48 h after post-inoculation (hpi). At the biochemical level, the activities of the enzymes chitinase (CHI), catalase (CAT) and allene oxide synthase (AOS) were significantly enhanced in trehalose-treated broccoli plants inoculated with A. brassicicola. The enzymatic activities were further validated by quantitative real-time polymerase chain reaction (qRT-PCR) analyses wherein the relative expressions of the corresponding gene transcripts were up-regulated in trehalose primed plants. Conclusively, the investigation results have provided vital insights into the histochemical, biochemical and gene expression underlying the enhanced induced systemic resistance against broccoli leaf spot disease.

Structural transitions in TPGS micelles induced by trehalose as a model cryoprotectant

Cryoprotectants are included to protect colloidal dispersions from mechanical stress of ice crystals formed at sub-zero temperature. Trehalose (THL) remains a popular choice among sugar-based cryoprotectants. In the present study, we illustrate the effect of THL concentration (0.01–1 M) upon microstructural characteristics of nonionic micelles which were formulated with alpha tocopherol polyethylene glycol 1000 succinate (TPGS). The effect of THL incorporation in drug-loaded micelles was studied by using capsaicin (CAP), a hydrophobic alkaloid. Our interpretations are based on the results of cloud point, dynamic light scattering (DLS), small angle neutron scattering (SANS), nuclear magnetic resonance (NMR) and Fourier-transformed infrared (FTIR) spectroscopic measurements. Cloud point and spectral data reveal that the micelles underwent progressive dehydration at increasing THL concentration. Together with scattering data, it is discernible that THL molecules intercalated in the micelle corona and expelled water from the polar headgroups. In spite of this, micelle size did not change until 1 M THL. Freeze-thawed micelles also displayed identical size distribution. Structural transitions occurred upon solubilization of CAP; micelles changed from sphere to ellipsoids. We suggest that CAP molecules occupied the hydrophobic core and triggered the formation of ellipsoids which were retained in the presence of THL. These observations lead us to a conclusion that, by virtue of its selective action (removal of freezable water) in headgroup region, THL protects the morphology of micelles over a wide concentration range.

PPE51 mediates uptake of trehalose across the mycomembrane of Mycobacterium tuberculosis

The disaccharide trehalose is essential for viability of Mycobacterium tuberculosis, which synthesizes trehalose de novo but can also utilize exogenous trehalose. The mycobacterial cell wall encompasses two permeability barriers, the cytoplasmic membrane and the outer mycolic acid-containing mycomembrane. The ABC transporter LpqY–SugA–SugB–SugC has previously been demonstrated to mediate the specific uptake of trehalose across the cytoplasmic membrane. However, it is still unclear how the transport of trehalose molecules across the mycomembrane is mediated. In this study, we harnessed the antimycobacterial activity of the analogue 6-azido trehalose to select for spontaneous resistant M. tuberculosis mutants in a merodiploid strain harbouring two LpqY–SugA–SugB–SugC copies. Mutations mediating resistance to 6-azido trehalose mapped to the proline–proline–glutamate (PPE) family member PPE51 (Rv3136), which has recently been shown to be an integral mycomembrane protein involved in uptake of low-molecular weight compounds. A site-specific ppe51 gene deletion mutant of M. tuberculosis was unable to grow on trehalose as the sole carbon source. Furthermore, bioorthogonal labelling of the M. tuberculosis Δppe51 mutant incubated with 6-azido trehalose corroborated the impaired internalization. Taken together, the results indicate that the transport of trehalose and trehalose analogues across the mycomembrane of M. tuberculosis is exclusively mediated by PPE51.

The Core–Shell Structure, Not Sugar, Drives the Thermal Stabilization of Single-Enzyme Nanoparticles

Trehalose is widely assumed to be the most effective sugar for protein stabilization, but exactly how unique the structure is and the mechanism by which it works are still debated. Herein, we use a polyion complex micelle approach to control the position of trehalose relative to the surface of glucose oxidase within cross-linked and non-cross-linked single-enzyme nanoparticles (SENs). The distribution and density of trehalose molecules in the shell can be tuned by changing the structure of the underlying polymer, poly(N-[3-(dimethylamino)propyl] acrylamide (PDMAPA). SENs in which the trehalose is replaced with sucrose and acrylamide are prepared as well for comparison. Isothermal titration calorimetry, dynamic light scattering, and asymmetric flow field-flow fraction in combination with multiangle light scattering reveal that two to six polymers bind to the enzyme. Binding either trehalose or sucrose close to the enzyme surface has very little effect on the thermal stability of the enzyme. By contrast, encapsulation of the enzyme within a cross-linked polymer shell significantly enhances its thermal stability and increases the unfolding temperature from 70.3 °C to 84.8 °C. Further improvements (up to 92.8 °C) can be seen when trehalose is built into this shell. Our data indicate that the structural confinement of the enzyme is a far more important driver in its thermal stability than the location of any sugar.

Role of Mono- and Disaccharide Combination in Cryoprotective Medium for Rooster Semen to Ensure Cryoresistance of Spermatozoa.

The combination of saccharides in the composition of a cryopreservation medium may represent a promising method for the preservation of the reproductive cells of male birds. In the current study, cryoprotective media with a combined composition of mono- and di-saccharides were developed. The degree of penetration of reducing saccharide molecules (maltose—Mal20 medium) and non-reducing disaccharide molecules (trehalose—Treh20 medium) from the cryoprotective medium into the cytosol of rooster spermatozoa was studied. LCM control media without disaccharides were used as the control. The number of maltose molecules penetrating from the outside into the cytosol of the spermatozoon was 1.06 × 104, and the number of trehalose molecules was 3.98 × 104. Using a combination of maltose and fructose, the progressive motility of frozen/thawed semen and the fertility rates of eggs were significantly higher ((p < 0.05) 40.2% and 68.5%, respectively) than when using a combination of trehalose and fructose in a cryoprotective diluent (33.4% and 62.4%, respectively). A higher rate of chromatin integrity at the level of 92.4% was obtained when using Treh20 versus 74.5% Mal20 (p < 0.05). Maltose positively affected the preservation of frozen/thawed sperm in the genital tract of hens. On the seventh day from the last insemination when using Mal20, the fertilization of eggs was 42.6% and only 27.3% when using Treh20. Despite the same molecular weight, maltose and trehalose have different physicochemical and biological properties that determine their function and effectiveness as components of cryoprotective media.

Thermoresponsivity of poly(N-isopropylacrylamide) microgels in water-trehalose solution and its relation to protein behavior

HypothesesAdditives are commonly used to tune macromolecular conformational transitions. Among additives, trehalose is an excellent bioprotectant and among responsive polymers, PNIPAM is the most studied material. Nevertheless, their interaction mechanism so far has only been hinted without direct investigation, and, crucially, never elucidated in comparison to proteins. Detailed insights would help understand to what extent PNIPAM microgels can effectively be used as synthetic biomimetic materials, to reproduce and study, at the colloidal scale, isolated protein behavior and its sensitivity to interactions with specific cosolvents or cosolutes. ExperimentsThe effect of trehalose on the swelling behavior of PNIPAM microgels was monitored by dynamic light scattering; Raman spectroscopy and molecular dynamics simulations were used to explore changes of solvation and dynamics across the swelling-deswelling transition at the molecular scale. FindingsStrongly hydrated trehalose molecules develop water-mediated interactions with PNIPAM microgels, thereby preserving polymer hydration below and above the transition while drastically inhibiting local motions of the polymer and of its hydration shell. Our study, for the first time, demonstrates that slowdown of dynamics and preferential exclusion are the principal mechanisms governing trehalose effect on PNIPAM microgels, at odds with preferential adsorption of alcohols, but in full analogy with the behavior observed in trehalose-protein systems.

Delving into controversial dichotomy of direct and indirect mechanisms of Trehalose: In search of unanimous consensus

Trehalose, a carbohydrate-based osmolyte, is a widely known protein stabilizer and aggregation inhibitor for numerous proteins. However, the origin of its mechanistic behavior is ambiguous, preventing its therapeutic applicability for broad range of diseases. The controversial reports of direct versus indirect mode of action of trehalose segregates it into two different branches with the potential to fit into both of them. The knowledge of the link connecting them is essential to dissect its placement and comprehensively describe the behavior of trehalose under different environmental conditions and on different proteins. In this regard, we have introspected trehalose’s direct and indirect interaction with residues of varying charge and nature, by simulating five physiologically relevant peptides containing acidic, basic, neutral, hydrophilic and hydrophobic amino acids respectively, and two proteins under different temperature conditions. It was observed that trehalose prefers to favorably bind with side chains of negatively charged acidic amino acid residues, irrespective of force field. The conjecture was validated by mutating these residues with neutral and hydrophobic groups, and was also substantiated by simulating full length proteins. In addition, existing biophysical experimental literature was explained in a different way as per our hypothesis. Ratio of exposed to total surface area of acidic amino acid residues is of prime importance. Trehalose’s perturbation to water molecules viz structural orientation and dynamical diffusion was found to be more in the hydration layer of trehalose. Thus, we propose that the indirect effect is prominent in the neighborhood of trehalose molecules, the distribution of which in turn is guided by direct interactions of trehalose with acidic patches on the protein surface. This way we have bridged the gap between the two hypotheses. We assert that the cause of trehalose’s mechanistic action towards protein stabilization and aggregation resides in its direct interaction with protein.

Impact of Altered Trehalose Metabolism on Physiological Response of Penicillium chrysogenum Chemostat Cultures during Industrially Relevant Rapid Feast/Famine Conditions

Due to insufficient mass transfer and mixing issues, cells in the industrial-scale bioreactor are often forced to experience glucose feast/famine cycles, mostly resulting in reduced commercial metrics (titer, yield and productivity). Trehalose cycling has been confirmed as a double-edged sword in the Penicillium chrysogenum strain, which facilitates the maintenance of a metabolically balanced state, but it consumes extra amounts of the ATP responsible for the repeated breakdown and formation of trehalose molecules in response to extracellular glucose perturbations. This loss of ATP would be in competition with the high ATP-demanding penicillin biosynthesis. In this work, the role of trehalose metabolism was further explored under industrially relevant conditions by cultivating a high-yielding Penicillium chrysogenum strain, and the derived trehalose-null strains in the glucose-limited chemostat system where the glucose feast/famine condition was imposed. This dynamic feast/famine regime with a block-wise feed/no feed regime (36 s on, 324 s off) allows one to generate repetitive cycles of moderate changes in glucose availability. The results obtained using quantitative metabolomics and stoichiometric analysis revealed that the intact trehalose metabolism is vitally important for maintaining penicillin production capacity in the Penicillium chrysogenum strain under both steady state and dynamic conditions. Additionally, cells lacking such a key metabolic regulator would become more sensitive to industrially relevant conditions, and are more able to sustain metabolic rearrangements, which manifests in the shrinkage of the central metabolite pool size and the formation of ATP-consuming futile cycles.

Mono- and dialdehyde of trehalose: new synthons to prepare trehalose bio-conjugates.

Trehalose, a non-reducing disaccharide of glucose, is a natural bioactive and non-toxic sugar. It is found in many organisms that synthesise it when their cells are exposed to stress conditions. While not produced by mammalian cells, this disaccharide and also some of its derivatives have been shown to have a number of interesting properties that indicate their importance in the treatment of certain human diseases. Differentiating the two glucosyl moieties in the trehalose molecule has often been a synthetic challenge. We report here an easy way to obtain the monoaldehyde of trehalose, as well as the relevant symmetrical dialdehyde. The reactivity of the aldehyde functionalities involved in the molecular structure of these synthons allows the easy preparation of the corresponding amino or carboxy derivatives of trehalose, as well the synthesis of some new trehalose conjugates useful for diagnostic or therapeutic purposes.

Influence of hydrophilic additives on the signal intensity in electrospray ionization of flavonoid glycosides.

The influence of hydrophilic additives glycine, glucose, and glycerol on electrospray ionization (ESI) signal intensity of flavonoid glycosides and a nonreducing disaccharide is examined. The addition of excess glycine to the ESI solution would affect signal intensity more than glucose and glycerol due to its strong hydration capability. The ESI signal response upon the addition of excess additives prepared was estimated in both selected ion monitoring and scan mode. All the mass spectrometry data were acquired in negative ion mode, because negative ion mode is recommended for saccharide compounds. The addition of glycine to the ESI solution of flavonoid glycosides and trehalose enhanced signal intensity, whereas the addition of glucose and glycerol had little effect. The signal intensity of rutin was higher than that of naringin and hesperidin, in accordance with their solubility in ESI solution. Trehalose molecules specifically interacted with glycine molecules to form a 1:1 trehalose-glycine complex, whereas the flavonoid glycosides did not produce such complex ions. The ESI signal enhancement of the saccharides with the additive glycine can be explained by its strong hydration capability, with the deprotonated carboxylic oxygens of zwitterionic glycine molecules strongly interacting with water hydrogen atoms resulting in strong hydration enthalpy. Consequently, glycine molecules set the analytes free from solvation with water molecules in the ESI droplets.

Ultraefficient stabilization of high internal phase emulsions by globular proteins in the presence of polyols: Importance of a core-shell nanostructure

We report that oil-in-water (o/w) high internal phase emulsions (HIPEs) can be ultra-efficiently stabilized by globular proteins in the presence of appropriate concentrations of polyols. Using bovine serum albumin (BSA) and trehalose as the model globular protein and polyol, stable HIPE gels at 0.8 oil volume fraction can be easily prepared at a protein concentration in the aqueous phase as low as 0.005 wt% in the presence of 40 wt% trehalose. Higher concentrations of polyols facilitated the formation of finer HIPEs with a stronger gel network associated with a higher extent of droplet bridging. The HIPE gels exhibited excellent coalescence stability against long-term storage or upon extensive heating. The ultra-efficient stabilization of BSA in the presence of trehalose arises from two contributions: facilitated formation of bridged emulsions and interfacial stabilization of trehalose aggregates. The soft particulate nature of BSA in the presence of trehalose was due to the formation of a core-shell nanostructure with trehalose molecules surrounding the protein core. The findings provide a novel and facile strategy to transform globular proteins into outstanding soft particles for stabilizing HIPEs, as well as guiding the development of novel biocompatible and even food-grade HIPEs with promising applications in the food, cosmetics and pharmaceutical fields.

Real-time monitoring of trehalose crystallization using quantum cascade laser microscopy and 2D-COS

Molecular detail of the trehalose crystallization process was obtained during thermal perturbation through real-time monitoring using a Quantum Cascade Laser (QCL) microscope and 2D correlation spectroscopy. We were able to separate QCL IR spectral data based on the hyperspectral images acquired into key segments that defined the crystallization events: (1) trehalose in solution or the pre-transition phase, (2) nucleation and crystallization transition and (3) the crystal growth phase. Furthermore, the hyperspectral images allowed for the determination of the region of interest (ROI) allowing for the selection of QCL IR spectral data directly associated with the crystallization process. This approach allowed for the distinction of different types of intermolecular Hydrogen bonding interactions and dynamics involving α,α-trehalose with its aqueous environment, the dihydrate and between trehalose molecules. To our knowledge this is the first time that a real-time description of the molecular events that lead to trehalose crystallization have been described.

Research on Antioxidant Properties of Several Marine Active Substances

Using DPPH free radical as an in vitro antioxidant model and using ascorbic acid (Vc) as a positive control, the four important marine activities of trehalose, carboxymethyl chitosan, glucosamine hydrochloride and corona bafil clam small molecule peptides were studied Antioxidant ability of the substance in vitro. The experimental results show that the four marine active substances have good antioxidant properties, and their antioxidant activity and concentration show a certain dose-effect relationship. The small molecular peptide of corrugated paphia is better at eliminating DPPH free radicals than the other two marine species. Active substance, when the concentration is 4 g/L, the elimination rate of DPPH radicals reaches 95.7447%.

Autophagy and Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease characterized by motor system dysfunction. The etiology of PD has been linked with aging, environmental toxins and genetic mutation, while molecular pathogenesis of PD includes various factors, such as impaired protein homeostasis, oxidative stress, mitochondria dysfunction, synaptic transmission impairment, calcium homeostasis imbalance, prion-like α-synuclein transmission and neuron inflammation. Autophagy is a conserved bulk degradation process to maintain cellular homeostasis. Impairment of autophagy has been reported to be involved in the pathogenesis of PD. Coding proteins of several PD-related genes, such as SNCA, LRRK2, GBA, ATP13A2, VPS35 and FBXO7, are implicated in or affected by autophagy process. Furthermore, various pathogenic events during PD directly or indirectly interfere with the autophagy pathway, and dysregulation of autophagy has been observed in different neurotoxic PD models. Autophagy has been regarded as a potential therapeutic target for PD treatment. Indeed, modulations of autophagy-regulated genes (BECN1 and TFEB) expression exerted neuroprotection against PD models, and various autophagy regulators, such as rapamycin, trehalose, lysosome modulators and other small molecule autophagy inducers, have displayed neuroprotective effects in experimental PD models. Taken together, autophagy dysfunction has been implicated in the pathogenesis of PD, and pharmacological modulation of autophagy may be a new therapeutic strategy for the PD treatment.