Animal Models Of Parkinson's Disease Research Articles

Neuroprotective and anti-inflammatory effects of the RIPK3 inhibitor GSK872 in an MPTP-induced mouse model of Parkinson’s disease

Parkinson's disease (PD) is a neurodegenerative disorder triggered by the loss of dopaminergic neurons in the substantia nigra (SN). Recent studies have demonstrated that necroptosis is involved in dopaminergic neuronal cell death and the resulting neuroinflammation. During the process of necroptosis, a necrosome complex is formed consisting of the proteins receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like protein (MLKL). Although the neuroprotective effects of the RIPK1-specific inhibitor necrostatin-1, as well as RIPK3 and MLKL knockout in mice, have been described, the effects of RIPK3 pharmacological inhibitors have not yet been reported in animal models of PD. In the present study, we investigated the neuroprotective effects of GSK872, a specific RIPK3 inhibitor, in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. GSK872 rescued MPTP-induced motor impairment and inhibited tyrosine hydroxylase-positive dopaminergic cell death in the SN and striatum. Additionally, GSK872 inhibited the MPTP-induced increase in the expression of p-RIPK3 and p-MLKL in both the dopaminergic neurons and microglia, as assessed by biochemical and histological analyses. GSK872 further inhibited microglial activation and the expression of inflammatory mediators including NLRP3, interleukin (IL)-1β, IL-6, tumor necrosis factor-alpha, and inducible nitric oxide synthase in the SN region of MPTP mice. Using in vitro experiments, we validated the effects of GSK872 on necroptosis in SH-SY5Y neuronal and BV2 microglial cells. Overall, our results suggest that GSK872 exerts neuroprotective and anti-inflammatory effects, and may thus have therapeutic potential for PD.

TAT-PPA1 protects against oxidative stress-induced loss of dopaminergic neurons.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra (SN) of the midbrain, resulting in severe motor impairments. Inorganic pyrophosphatase 1 (PPA1) plays a key role in various biological processes, and this study introduces a cell-penetrating PPA1 fusion protein (TAT-PPA1) to explore its transduction into cells and brain tissues. TAT-PPA1 effectively penetrates SH-SY5Y cells and the SN region of PD animal models without toxicity, exhibiting protective effects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP-)-induced cell death. TAT-PPA1 revealed an inhibitory influence on the MAPK signaling pathway and MPTP-induced reactive oxygen species (ROS) production. TAT-PPA1 suppresses JNK, AKT, p53, ERK, and p38 phosphorylation, showcasing its multifaceted role in cell survival pathways. In the MPTP-induced PD animal model, TAT-PPA1 prevents dopaminergic cell death and enhances motor function. This study shows that TAT-PPA1 protects against oxidative stress and cell death in neurodegenerative diseases, suggesting potential as a PD treatment.

Virus-like Particles-Based Vaccine to Combat Neurodegenerative Diseases.

Neurodegenerative diseases are regarded as gradual, incurable conditions with an insidious onset. Alzheimer's disease (AD) and Parkinson's disease (PD) are two of the most prevalent neurodegenerative diseases reported globally. Developing effective treatment strategies for neurodegenerative diseases has remained a primary objective and a huge challenge for researchers. The therapeutic medications that are now approved for the treatment of neurodegenerative diseases merely treat the symptoms; the underlying pathology is not addressed. Therefore, the emergence of novel disease-modifying therapeutic modalities such as immunotherapy has opened a new path in developing effective treatments for neurogenerative diseases. Compared to other types of subunit active vaccines, virus-like particles (VLPs) are considerably more immunogenic as they present dense and repetitive viral antigen epitopes on their surface, which can trigger both humoral and cell-mediated immune responses. They are also a much safer option than the traditional inactivated and live-attenuated vaccines since they are devoid of viral genomes and are, therefore, non-pathogenic and non-infectious. Researchers have turned their attention to VLPs as an active immunotherapy candidate for AD due to the lessons learned from the AN1792 trial. Studies have shown that they effectively induce anti-Aβ, anti-tau, and anti-α-Synuclein antibodies while avoiding T-cell-related immune reactions in animal models of AD and PD. This review compiles the findings of preclinical animal model studies and clinical investigations on VLP-based vaccines for neurogenerative diseases thus far. The technical limitations and potential difficulties associated with the future application of VLP-based vaccines in patients with neurodegenerative diseases have also been covered.

Behavioral disorders in Parkinson disease: current view.

Patients with Parkinson disease (PD) frequently experience several behavioral symptoms, such as anxiety, apathy, irritability, agitation, impulsive control and obsessive-compulsive or REM sleep behavior disorders, which can cause severe psychosocial problems and impair quality of life. Occurring in 30-70% of PD patients, these symptoms can manifest at early stages of the disease, sometimes even before the appearance of classic motor symptoms, while others can develop later. Behavioral changes in PD show distinct patterns of brain atrophy, dopaminergic and serotonergic deterioration, altered neuronal connectivity in frontostriatal, corticolimbic, default mode and other networks due to a cascade linking molecular pathologies and deficits in multiple behavior domains. The changes suggest a multi-system neurodegenerative process in the context of a specific α-synucleinopathy inducing a variety of biochemical and functional changes, the neurobiological basis and clinical relevance of which await further elucidation. This paper is intended to review the recent literature with focus on the main behavioral disturbances in PD patients, their epidemiology, clinical features, risk factors, animal models, neuroimaging findings, pathophysiological backgrounds, and treatment options of these deleterious lesions.

Potential Neuroprotective Effects of Alpinia officinarum Hance (Galangal): A Review.

Background/Objectives: This review aims to provide a detailed understanding of the current evidence on Alpinia officinarum Hance (A. officinarum) and its potential therapeutic role in central nervous system (CNS) disorders. CNS disorders encompass a wide range of disorders affecting the brain and spinal cord, leading to various neurological, cognitive and psychiatric impairments. In recent years, natural products have emerged as potential neuroprotective agents for the treatment of CNS disorders due to their outstanding bioactivity and favourable safety profile. One such plant is A. officinarum, also known as lesser galangal, a perennial herb from the Zingiberaceae family. Its phytochemical compounds such as flavonoids and phenols have been documented to have a powerful antioxidants effect, capable of scavenging free radicals and preventing oxidative damage. Methods: In this review, we critically evaluate the in vitro and in vivo studies and examine the mechanisms by which A. officinarum exerts its neuroprotective effect. Results: Several studies have confirmed that A. officinarum exerts its neuroprotective effects by reducing oxidative stress and cell apoptosis, promoting neurite outgrowth, and modulating neurotransmitter levels and signalling pathways. Conclusions: Although previous studies have shown promising results in various models of neurological disorders, the underlying mechanisms of A. officinarum in Alzheimer's (AD) and Parkinson's disease (PD) are still poorly understood. Further studies on brain tissue and cognitive and motor functions in animal models of AD and PD are needed to validate the results observed in in vitro studies. In addition, further clinical studies are needed to confirm the safety and efficacy of A. officinarum in CNS disorders.

Protective and Damaging Mechanisms of Neuromelanin-Like Nanoparticles and Iron in Parkinson's Disease.

Parkinson's disease (PD) pathology speculates that neuromelanin (NM) and iron ions play a significant role in physiological and pathological conditions of PD. Because the difficult accessibility of NM has limited targeted research, synthetic melanin-like nanoparticles have been used to instead. In this report, the eumelanin and pheomelanin-like polydopamine (PDA) nanoparticles are prepared that can be used to simulate natural NM with or without chelating iron ion and studied the redox effects in vitro and in vivo on neuronal cells and PD. The synthetic pheomelanin-like PDA nanoparticles have much stronger redox activity than eumelanin-like PDA nanoparticles without or with iron ion. They can protect neurons by scavenging reactive oxygen species (ROS), while cause neuronal cell death and PD due to excessive binding of iron ions. This work provides new evidence for the relationship among two structural components of NM and iron in PD as well as displays the different effects on the roles of eumelanin and pheomelanin in redox activity under physiological or pathological conditions, which provide a new effective choice for cellular and animal models of PD and offer theoretical guidance for targeted treatment and mechanism research on PD.

Modeling of Parkinson's Disease in Different Models.

Parkinson's Disease (PD) is a progressive disorder worldwide and its etiology remains unidentified. Over the last few decades, animal models of PD have been extensively utilized to explore the development and mechanisms of this neurodegenerative condition. Toxic and transgenic animal models for PD possess unique characteristics and constraints, necessitating careful consideration when selecting the appropriate model for research purposes. Animal models have played a significant role in uncovering the causes and development of PD, including its cellular and molecular processes. These models suggest that the disorder arises from intricate interplays between genetic predispositions and environmental influences. Every model possesses its unique set of strengths and weaknesses. This review provides a critical examination of animal models for PD and compares them with the features observed in the human manifestation of the disease.

Exercise, Neuroprotective Exerkines, and Parkinson's Disease: A Narrative Review.

Parkinson's disease (PD) is a prevalent neurodegenerative disease in which treatment often includes an exercise regimen. Exercise is neuroprotective in animal models of PD, and, more recently, human clinical studies have verified exercise's disease-modifying effect. Aerobic exercise and resistance training improve many of PD's motor and non-motor symptoms, while neuromotor therapy and stretching/flexibility exercises positively contribute to the quality of life in people with PD. Therefore, understanding the role of exercise in managing this complex disorder is crucial. Exerkines are bioactive substances that are synthesized and released during exercise and have been implicated in several positive health outcomes, including neuroprotection. Exerkines protect neuronal cells in vitro and rodent PD models in vivo. Aerobic exercise and resistance training both increase exerkine levels in the blood, suggesting a role for exerkines in the neuroprotective theory. Many exerkines demonstrate the potential for protecting the brain against pathological missteps caused by PD. Every person (people) with Parkinson's (PwP) needs a comprehensive exercise plan tailored to their unique needs and abilities. Here, we provide an exercise template to help PwP understand the importance of exercise for treating PD, describe barriers confronting many PwP in their attempt to exercise, provide suggestions for overcoming these barriers, and explore the role of exerkines in managing PD. In conclusion, exercise and exerkines together create a powerful neuroprotective system that should contribute to slowing the chronic progression of PD.

Nrf2 Deficiency Exacerbates Parkinson's Disease by Aggravating NLRP3 Inflammasome Activation in MPTP-Induced Mouse Models and LPS-Induced BV2 Cells.

Parkinson's disease (PD) is a movement disorder characterized by the progressive loss of dopamine neurons. Microglia-mediated neuroinflammation drives disease progression and becomes a critical factor in neuronal degeneration. Recent studies have found that nuclear factor-erythroid 2-related-2 (Nrf2) expression levels are reduced during aging and neurodegenerative diseases, but its regulatory mechanism on microglia-induced neuroinflammation has not been fully elucidated. In vivo, we used the intraperitoneal injection of the neurotoxic drug neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to establish an animal model of PD and, at the same time, administered Nrf2 inhibitors ML385 and dimethyl fumarate to regulate Nrf2 protein levels. In vitro, we used si-RNA to knock out the Nrf2 gene to intervene in BV2 cells and used lipopolysaccharide (LPS) to stimulate and induce the cell model. The study found that inhibition of Nrf2 expression aggravated the motor defects of PD mice, accompanied by a significant loss of dopaminergic neurons in the substantia nigra and striatum of the brain. In addition, after inhibition of Nrf2, the malondialdehyde (MDA) level in the substantia nigra of the midbrain of mice increased, and the levels of superoxide dismutase (SOD) and heme oxygenase-1 (HO-1) decreased, accompanied by the proliferation of microglia and astrocytes. In addition, the activation of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome, the assembly of apoptosis-associated speck-like protein containing a CARD (ASC) protein in microglia, and the release of downstream inflammatory factors caspase-1 and interleukin (IL)-1β, were aggravated. At the cellular level, it was found that knocking out the expression of Nrf2 would aggravate the activation of NLRP3 inflammasomes and the assembly of ASC in LPS-induced BV2 cells. Inhibited Nrf2 activity can reduce the downstream antioxidant enzyme HO-1 and antioxidant levels, induce NLRP3 inflammasome activation and ASC protein assembly in microglia, and ultimately aggravate PD inflammatory response and dopamine neuron degeneration.

The Interplay of Carveol and All-Trans Retinoic Acid (ATRA) in Experimental Parkinson's Disease: Role of Inflammasome-Mediated Pyroptosis and Nrf2.

Parkinson's disease (PD) is a debilitating and the second most common neurodegenerative disorder with a high prevalence. PD has a multifaceted etiology characterized by an altered redox state and an excessive inflammatory response. Extensive research has consistently demonstrated the role of the nuclear factor E2-related factor (Nrf2) and inflammasomes, notably NLRP3 in neurodegenerative diseases. In this study, our focus was on exploring the potential neuroprotective properties of carveol in Parkinson's disease. Our findings suggest that carveol may exhibit these effects through Nrf2 and by suppressing pyroptosis. Male albino mice were treated with carveol, and the animal PD model was induced through a single intranigral dose of 2µg/2µl lipopolysaccharide (LPS). To further demonstrate the essential role of the Nrf2 pathway, we utilized all-trans retinoic acid (ATRA) to inhibit the Nrf2. Our finding showed the induction of pyroptosis as evidenced by increased levels of NLRP3 and other inflammatory mediators, including IL-1β, iNOS, p-NFKB, and apoptotic cell death indicated by positive fluoro Jade B (FJB) staining. Moreover, increased levels of lipid peroxides and reactive oxygen species indicated a significant rise in oxidative stress due to LPS. The administration of carveol mitigates oxidative stress and suppresses inflammatory pathways through the augmentation of intrinsic antioxidant defenses, primarily via the activation of the Nrf2. Conversely, ATRA reversed carveol protective effects by increasing FJB-positive cells, inflammatory and oxidative biomarkers. Taken together, our findings suggest that carveol mitigated LPS-induced Parkinson-like symptoms, partially through the activation of the Nrf2 and downregulation of pyroptosis notably NLRP3.

Mitochondrial stress-induced H4K12 hyperacetylation dysregulates transcription in Parkinson's disease.

Aberrant epigenetic modification has been implicated in the pathogenesis of Parkinson's disease (PD), which is characterized by the irreversible loss of dopaminergic (DAergic) neurons. However, the mechanistic landscape of histone acetylation (ac) in PD has yet to be fully explored. Herein, we mapped the proteomic acetylation profiling changes at core histones H4 and thus identified H4K12ac as a key epigenomic mark in dopaminergic neuronal cells as well as in MitoPark animal model of PD. Notably, the significantly elevated H4K12ac deposition in post-mortem PD brains highlights its clinical relevance to human PD. Increased histone acetyltransferase (HAT) activity and decreased histone deacetylase 2 (HDAC2) and HDAC4 were found in experimental PD cell models, suggesting the HAT/HDAC imbalance associated with mitochondrial stress. Following our delineation of the proteasome dysfunction that possibly contributes to H4K12ac deposition, we characterized the altered transcriptional profile and disease-associated pathways in the MitoPark mouse model of PD. Our study uncovers the axis of mitochondrial impairment-H4K12ac deposition-altered transcription/disease pathways as a neuroepigenetic mechanism underlying PD pathogenesis. These findings provide mechanistic information for the development of potential pharmacoepigenomic translational strategies for PD.

BDNF-Regulated Modulation of Striatal Circuits and Implications for Parkinson's Disease and Dystonia.

Neurotrophins, particularly brain-derived neurotrophic factor (BDNF), act as key regulators of neuronal development, survival, and plasticity. BDNF is necessary for neuronal and functional maintenance in the striatum and the substantia nigra, both structures involved in the pathogenesis of Parkinson's Disease (PD). Depletion of BDNF leads to striatal degeneration and defects in the dendritic arborization of striatal neurons. Activation of tropomyosin receptor kinase B (TrkB) by BDNF is necessary for the induction of long-term potentiation (LTP), a form of synaptic plasticity, in the hippocampus and striatum. PD is characterized by the degeneration of nigrostriatal neurons and altered striatal plasticity has been implicated in the pathophysiology of PD motor symptoms, leading to imbalances in the basal ganglia motor pathways. Given its essential role in promoting neuronal survival and meditating synaptic plasticity in the motor system, BDNF might have an important impact on the pathophysiology of neurodegenerative diseases, such as PD. In this review, we focus on the role of BDNF in corticostriatal plasticity in movement disorders, including PD and dystonia. We discuss the mechanisms of how dopaminergic input modulates BDNF/TrkB signaling at corticostriatal synapses and the involvement of these mechanisms in neuronal function and synaptic plasticity. Evidence for alterations of BDNF and TrkB in PD patients and animal models are reviewed, and the potential of BDNF to act as a therapeutic agent is highlighted. Advancing our understanding of these mechanisms could pave the way toward innovative therapeutic strategies aiming at restoring neuroplasticity and enhancing motor function in these diseases.

AAV-aMTD-Parkin, a therapeutic gene delivery cargo, enhances motor and cognitive functions in Parkinson's and Alzheimer’s diseases

Neurodegenerative disorders, such as Parkinson's disease (PD) and Alzheimer's disease (AD), have a global prevalence and profoundly impact both motor and cognitive functions. Although adeno-associated virus (AAV)-based gene therapy has shown promise, its application for treating central nervous system (CNS) diseases faces several challenges, including effective delivery of AAV vectors across the blood-brain barrier, determining optimal dosages, and achieving targeted distribution. To address these challenges, we have developed a fusion delivery therapeutic cargo called AAV-aMTD-Parkin, which combines a hydrophobic cell-penetrating peptide sequence with the DNA sequences of AAV and Parkin. By employing this fusion delivery platform at lower dosages compared to zolgensma, we have achieved significant enhancements in cell and tissue permeability, while reducing the occurrence of common pathological protein aggregates. Consequently, motor and cognitive functions were restored in animal models of PD and AD. With its dual functionality in addressing PD and AD, AAV-aMTD-Parkin holds immense potential as a novel class of therapeutic biologics for prevalent CNS diseases.

LncRNA SOX21-AS1 Promotes Activation of BV2 Cells via Epigenetical Silencing of SOCS3 and Aggravates Parkinson’s Disease

Background: LncRNAs perform a crucial impact on microglia’s activation in Parkinson’s disease (PD). Here, our purpose was to probe the function and involved mechanism of lncRNA SOX21-AS1 on microglial activation in PD. Methods: Mice were treated with MPTP, and BV2 cells were treated with LPS/ATP to build PD animal and cell models. Genes’ expression was measured using RT-qPCR, immunoblotting, and IHC stain. ELISA was applied for testing inflammatory factors’ levels. Cell viability and apoptosis were tested using kits. RIP and RNA pull-down assay were utilized for monitoring the bond of SOX21-AS1 to EZH2, and ChIP was applied for affirming the bond between EZH2 and SOCS3’s promoter. Results: The expression of SOX21-AS1 and SOCS3 was abnormal in PD cell and animal models. Inhibition of SOX21-AS1 repressed LPS/ATP-induced activation in BV2 cells and nerve damage caused by activated BV2 cells, alleviating the pathological features of PD mice. Further studies found that SOX21-AS1 epigenetically inhibited SOCS3 by recruiting EZH2 to SOCS3 promoter. SOX21-AS1 overexpression partially offset the repressive impact of SOCS3 enhancement on BV2 cell activation and the protective effect on nerve cells. Conclusion: SOX21-AS1 enhances LPS/ATP-induced activation of BV2 cells and nerve damage caused by activated BV2 cells though recruiting EZH2 to SOCS3’s promoter, thereby alleviating PD progression. Our research supplies new potential target for curing PD.

Pterostilbene alleviates MPTP-induced neurotoxicity by targeting neuroinflammation and oxidative stress

Pterostilbene (PTE), a naturally occurring phenolic compound primarily found in blueberries, demonstrates neuroprotective properties. However, the role of PTE in Parkinson's disease (PD) remains unclear. This study aimed to investigate the neuroprotective role of PTE in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD animal model. Our findings demonstrate that administering PTE effectively reversed the diminished levels of dopamine in the striatum, thereby ameliorating motor impairments in the MPTP model. Moreover, PTE administration mitigated the loss of dopaminergic (DA) neurons and reduced the upregulation of α-synuclein (α-syn) induced by MPTP. Mechanistic analysis revealed that PTE administration inhibited the activation of microglia and astrocytes, as well as pro-inflammatory factors such as TNF-α and IL-1β in the MPTP model. Additionally, PTE administration decreased MPTP-induced levels of reactive oxygen species (ROS) and malondialdehyde (MDA), while increasing total antioxidant capacity (TAOC) and superoxide dismutase (SOD) activity, thereby attenuating oxidative stress. Collectively, these findings demonstrate that PTE exerts neuroprotective effects in the MPTP mouse model of PD by suppressing neuroinflammation and oxidative stress. Thus, PTE holds promise as a therapeutic agent for PD.

The protective effects of repetitive transcranial magnetic stimulation with different high frequencies on motor functions in MPTP/probenecid induced Parkinsonism mouse models.

High-frequency repeated transcranial magnetic stimulation (rTMS) stimulating the primary motor cortex (M1) is an alternative, adjunctive therapy for improving the motor symptoms of Parkinson's disease (PD). However, whether the high frequency of rTMS positively correlates to the improvement of motor symptoms of PD is still undecided. By controlling for other parameters, a disease animal model may be useful to compare the neuroprotective effects of different high frequencies of rTMS. The current exploratory study was designed to compare the protective effects of four common high frequencies of rTMS (5, 10, 15, and 20Hz) and iTBS (a special form of high-frequency rTMS) and explore the optimal high-frequency rTMS on an animal PD model. Following high frequencies of rTMS application (twice a week for 5weeks) in a MPTP/probenecid-induced chronic PD model, the effects of the five protocols on motor behavior as well as dopaminergic neuron degeneration levels were identified. The underlying molecular mechanisms were further explored. We found that all the high frequencies of rTMS had protective effects on the motor functions of PD models to varying degrees. Among them, the 10, 15, and 20Hz rTMS interventions induced comparable preservation of motor function through the protection of nigrostriatal dopamine neurons. The enhancement of brain-derived neurotrophic factor (BDNF), dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT-2)and the suppression of TNF-α and IL-1β in the nigrostriatum were involved in the process. The efficacy of iTBS was inferior to that of the above three protocols. The effect of 5Hz rTMS protocol was weakest. Combined with the results of the present study and the possible side effects induced by rTMS, we concluded that 10Hz might be the optimal stimulation frequency for preserving the motor functions of PD models using rTMS treatment.

Nicotinamide riboside first alleviates symptoms but later downregulates dopamine metabolism in proteasome inhibition mouse model of Parkinson's disease

Parkinson's disease (PD) is associated with a reduction in 26/20S proteasome and mitochondrial function and depletion of dopamine. Activation of mitochondrial function with the NAD+ precursor nicotinamide riboside (NR) is a potential therapeutic for PD. However, despite recently started clinical trials, analysis of NR in mammalian animal PD models is lacking and data in simpler PD models is limited. We analyzed the effect of NR in C. elegans and in mouse 26/20S proteasome inhibition models of PD. In C. elegans, NR rescued α-synuclein overexpression induced phenotypes likely by activating the mitochondrial unfolded protein response. However, in a proteasome inhibitor-induced mouse model of PD, NR first partially rescued behavioural dysfunction, but later resulted in decrease in dopamine and its related gene expression in the substantia nigra. Our results suggest that reduction in 26/20S function with long term NR treatment may increase risk for developing reduced nigrostriatal DA function.

Unlocking the Potential: Semaglutide's Impact on Alzheimer's and Parkinson's Disease in Animal Models.

Semaglutide (SEM), a glucagon-like peptide-1 receptor agonist, has garnered increasing interest for its potential therapeutic effects in neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). This review provides a comprehensive description of SEM's mechanism of action and its effects in preclinical studies of these debilitating conditions. In animal models of AD, SEM has proved beneficial effects on multiple pathological hallmarks of the disease. SEM administration has been associated with reductions in amyloid-beta plaque deposition and mitigation of neuroinflammation. Moreover, SEM treatment has been shown to ameliorate behavioral deficits related to anxiety and social interaction. SEM-treated animals exhibit improvements in spatial learning and memory retention tasks, as evidenced by enhanced performance in maze navigation tests and novel object recognition assays. Similarly, in animal models of PD, SEM has demonstrated promising neuroprotective effects through various mechanisms. These include modulation of neuroinflammation, enhancement of mitochondrial function, and promotion of neurogenesis. Additionally, SEM has been shown to improve motor function and ameliorate dopaminergic neuronal loss, offering the potential for disease-modifying treatment strategies. Overall, the accumulating evidence from preclinical studies suggests that SEM holds promise as a novel therapeutic approach for AD and PD. Further research is warranted to elucidate the underlying mechanisms of SEM's neuroprotective effects and to translate these findings into clinical applications for the treatment of these devastating neurodegenerative disorders.

The role of autophagy in Parkinson's disease: a gender difference overview.

Recent studies have demonstrated dysregulation of the autophagy pathway in patients with Parkinson's disease (PD) and in animal models of PD, highlighting its emerging role in disease. In particular, several studies indicate that autophagy, which is an essential degradative process for the damaged protein homeostasis and the management of cell balance, can manifest significant variations according to gender. While some evidence suggests increased autophagic activation in men with PD, women may have distinct regulatory patterns. In this review, we examined the existing literature on gender differences in PD-associated autophagic processes, focusing on the autophagy related proteins (ATGs) and leucine rich repeat kinase 2 (LRRK2) genes. Also, this review would suggest that an in-depth understanding of these gender differences in autophagic processes could open new perspectives for personalized therapeutic strategies, promoting more effective and targeted management of PD.

Rhein alleviates MPTP-induced Parkinson's disease by suppressing neuroinflammation via MAPK/IκB pathway.

Parkinson's disease (PD) is a common neurodegenerative disease with a rapid increase in incidence in recent years. Existing treatments cannot slow or stop the progression of PD. It was proposed that neuroinflammation leads to neuronal death, making targeting neuroinflammation a promising therapeutic strategy. Our previous studies have demonstrated that rhein protects neurons in vitro by inhibiting neuroinflammation, and it has been found to exhibit neuroprotective effects in Alzheimer's disease and epilepsy, but its neuroprotective mechanisms and effects on PD are still unclear. PD animal model was induced by 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP). ELISA, RT-qPCR, western blot and Immunofluorescence were used to detect the levels of inflammatory cytokines and M1 polarization markers. The protein expression levels of signaling pathways were measured by western blot. Hematoxylin-eosin (HE) staining showed that rhein did not damage the liver and kidney. Two behavioral tests, pole test and rotarod test, were used to evaluate the improvement effect of rhein on movement disorders. The number of neurons in the substantia nigra was evaluated by Nissl staining. Immunohistochemistry and western blot were used to detect tyrosine hydroxylase (TH) and α-synuclein. Rhein inhibited the activation of MAPK/IκB signaling pathway and reduced the levels of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and M1 polarization markers of microglia in vivo. In a mouse model of PD, rhein ameliorated movement disorders, reduced dopaminergic neuron damage and α-synuclein deposition. Rhein inhibits neuroinflammation through MAPK/IκB signaling pathway, thereby reducing neurodegeneration, α-synuclein deposition, and improving movement disorders in Parkinson's disease.