Erythrocytic α-Synuclein and the Gut Microbiome: Kindling of the Gut-Brain Axis in Parkinson's Disease.

Background: Progressive spreading of α-synuclein via gut-brain axis has been hypothesized in the pathogenesis of Parkinson's disease (PD). However, the source of seeding-capable α-synuclein in the gastrointestinal tract (GIT) has not been fully investigated. Additionally, the mechanism by which the GIT microbiome contributes to PD pathogenesis remains to be characterized.

GV-971 attenuates α-Synuclein aggregation and related pathology.

Rationale: Synucleinopathies, including Parkinson's disease (PD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB), share a distinct pathological feature, that is, a widespread accumulation of α-synuclein (α-syn) in the brain. There is a significant clinical unmet need for disease-modifying treatments for synucleinopathies. Recently, a seaweed-derived mixture of oligosaccharides sodium oligomannate, GV-971, was approved for Phase 2 clinical trials for PD.

The cervical lymph node contributes to peripheral inflammation related to Parkinson's disease.

Background: Peripheral inflammation is an important feature of Parkinson's disease (PD). However, if and how CNS pathology is involved in the peripheral inflammation in PD remains to be fully investigated. Recently, the existence of meningeal lymphatics and its involvement in draining cerebral spinal fluid (CSF) to the cervical lymph node has been discovered.

Parkinson's Disease Derived Exosomes Aggravate Neuropathology in SNCA*A53T Mice.

Objective: Accumulation of α-synuclein (α-syn) in neurons is a prominent feature of Parkinson's disease (PD). Recently, researchers have considered that extracellular vesicles (EVs) may play an important role in protein exportation and propagation, and α-syn-containing EVs derived from the central nervous system (CNS) have been detected in peripheral blood. However, mechanistic insights into CNS-derived EVs have not been well-described.

Exosomal microRNAs induce tumor-associated macrophages via PPARγ during tumor progression in SHH medulloblastoma.

Medulloblastoma (MB), the most common malignant pediatric brain tumor, is composed of at least four molecular subgroups with distinct clinical characteristics. The sonic hedgehog (SHH) subgroup exhibits the most abundant tumor-associated microglia/macrophages (TAMs) infiltration. SHH-MB patients treated by anti-SHH drugs showed high drug resistance.

α-Synuclein-containing erythrocytic extracellular vesicles: essential contributors to hyperactivation of monocytes in Parkinson's disease.

Background: Immune system dysfunction, including higher levels of peripheral monocytes and inflammatory cytokines, is an important feature of Parkinson's disease (PD) pathogenesis, although the mechanism underlying the process remains to be investigated. In the central nervous system, it is well-known that α-synuclein (α-syn), a key protein involved in PD, activates microglia potently, and it is also reported that α-syn exists in the peripheral system, especially in erythrocytes or red blood cells (RBC) at exceedingly high concentration. The current study focused on the possibility that RBC-derived α-syn mediates the sensitization of peripheral monocytes in PD patients.

Astrocytic VEGFA: An essential mediator in blood-brain-barrier disruption in Parkinson's disease.

The integrity of blood-brain-barrier (BBB) is essential for normal brain functions, synaptic remodeling, and angiogenesis. BBB disruption is a common pathology during Parkinson's disease (PD), and has been hypothesized to contribute to the progression of PD. However, the molecular mechanism of BBB disruption in PD needs further investigation.

EV PD-L1 Contributes to Immunosuppressive CD8 T Cells in Peripheral Blood of Pediatric Wilms Tumor.

Wilms tumor (WT) is the most common renal cancer and the most prevalent abdominal cancer in children. Children with recurrent or progressive forms of WT could benefit from novel immune-targeted approaches. While the immune status of these patients, especially the immunosuppression of peripheral T cells, was rarely reported.

Enhanced Antitumor Immune Responses via a Self-Assembled Carrier-Free Nanovaccine.

Nanovaccines have emerged as promising agents for cancer immunotherapy. However, insufficient antitumor immunity caused by inefficient antigen/adjuvant loading and complicated preparation processes are the major obstacles that limit their clinical application. Herein, two adjuvants, monophosphatidyl A (MPLA) and CpG ODN, with antigens were designed into a nanovaccine to overcome the above obstacles.

Reduced erythrocytic CHCHD2 mRNA is associated with brain pathology of Parkinson's disease.

Peripheral biomarkers indicative of brain pathology are critically needed for early detection of Parkinson's disease (PD). In this study, using NanoString and digital PCR technologies, we began by screening for alterations in genes associated with PD or atypical Parkinsonism in erythrocytes of PD patients, in which PD-related changes have been reported, and which contain ~ 99% of blood α-synuclein. Erythrocytic CHCHD2 mRNA was significantly reduced even at the early stages of the disease.

Erythrocytic α-synuclein contained in microvesicles regulates astrocytic glutamate homeostasis: a new perspective on Parkinson's disease pathogenesis.

Parkinson's disease is a neurodegenerative disorder characterized by the transmission and accumulation of toxic species of α-synuclein (α-syn). Extracellular vesicles (EVs) are believed to play a vital role in the spread of toxic α-syn species. Recently, peripheral α-syn pathology has been investigated, but little attention has been devoted to erythrocytes, which contain abundant α-syn.

Extracellular microvesicles-derived from microglia treated with unaggregated α-synuclein attenuate mitochondrial fission and toxicity-induced by Parkinsonian toxin MPP.

Biological functions of extracellular vesicles (EVs) are being discovered to be critical in neurodegenerative disorders, including Parkinson's disease (PD). A previous study using cellular models of PD has suggested that EVs derived from microglia exposed to aggregated α-synuclein (α-Syn) leads to enhanced neurotoxicity. However, the function of EVs derived from microglia not treated with aggregated a-Syn or treated with monomeric α-Syn are unclear.

Study of the enantioselectivity and recognition mechanism of chiral dual system based on chondroitin sulfate D in capillary electrophoresis.

Several chiral reagents including cyclodextrins (CDs) and derivatives, crown ethers, proteins, chiral surfactants, and polymers have been involved in dual-selector systems for enantioseparation of a series of compounds by capillary electrophoresis (CE). In this paper, chondroitin sulfate D-based dual-selector system (CSD/CM-β-CD) was firstly established and investigated for the enantioseparation of six basic racemic drugs in capillary electrophoresis. Compared to the single-selector systems, synergistic effect and significantly improved separations for all tested analytes were observed in CSD/CM-β-CD system.

Synthesis and application of ionic liquid functionalized β-cyclodextrin, mono-6-deoxy-6-(4-amino-1,2,4-triazolium)-β-cyclodextrin chloride, as chiral selector in capillary electrophoresis.

Recently,ionic liquids (ILs) functionalized cyclodextrins (CDs) have attracted more and more attention in the fields of enantioseparation. In this study, a novel IL amino triazolium functionalized β-CD derivative, mono-6-deoxy-6-(4-amino-1,2,4-triazolium)-β-cyclodextrin chloride (4-ATMCDCl), was synthesized for the first time and managed to separate dansyl amino acids and naproxen by capillary electrophoresis (CE). Compared with native β-CD, the new selector exhibited good water solubility and enhanced enantioselectivity.

Establishment and molecular modeling study of maltodextrin-based synergistic enantioseparation systems with two new hydroxy acid chiral ionic liquids as additives in capillary electrophoresis.

Discovering more superior performance of ionic liquids for the separation science has triggered increasing interest. In this work, two new Hydroxy acid-based chiral ionic liquids (CILs) (tertramethylammonium-d-pantothenate (TMA-d-PAN), tertramethylammonium-d-quinate (TMA-d-QUI)) were designed and first used as additives to establish the maltodextrin-based synergistic systems for enantioseparation in capillary electrophoresis (CE). Compared to traditional single maltodextrin chiral separation system, significantly improved separations of all tested drugs in the CIL/Maltodextrin synergistic systems were obtained.