Role of microglial metabolic reprogramming in Parkinson's disease.

Parkinson's disease (PD) is a common age-related neurodegenerative disorder characterized by damage to nigrostriatal dopaminergic neurons. Key pathogenic mechanisms underlying PD include alpha-synuclein misfolding and aggregation, impaired protein clearance, mitochondrial dysfunction, oxidative stress, and neuroinflammation. However, to date, no study has confirmed the specific pathogenesis of PD. Similarly, current PD treatment methods still have shortcomings. Although some emerging therapies have proved effective for PD, the specific mechanism still needs further clarification. Metabolic reprogramming, a term first proposed by Warburg, is applied to the metabolic energy characteristics of tumor cells. Microglia have similar metabolic characteristics. Pro-inflammatory M1 type and anti-inflammatory M2 type are the two types of activated microglia, which exhibit different metabolic patterns in glucose, lipid, amino acid, and iron metabolism. Additionally, mitochondrial dysfunction may be involved in microglial metabolic reprogramming by activating various signaling mechanisms. Functional changes in microglia resulting from metabolic reprogramming can cause changes in the brain microenvironment, thus playing an important role in neuroinflammation or tissue repair. The involvement of microglial metabolic reprogramming in PD pathogenesis has been confirmed. Neuroinflammation and dopaminergic neuronal death can effectively be reduced by inhibiting certain metabolic pathways in M1 microglia or reverting M1 cells to the M2 phenotype. This review summarizes the relationship between microglial metabolic reprogramming and PD and provides strategies for PD treatment.

Recent research progress on metabolic syndrome and risk of Parkinson's disease.

Parkinson's disease (PD) is one of the most widespread neurodegenerative diseases. PD is associated with progressive loss of substantia nigra dopaminergic neurons, including various motor symptoms (e.g., bradykinesia, rigidity, and resting tremor), as well as non-motor symptoms (e.g., cognitive impairment, constipation, fatigue, sleep disturbance, and depression). PD involves multiple biological processes, including mitochondrial or lysosomal dysfunction, oxidative stress, insulin resistance, and neuroinflammation. Metabolic syndrome (MetS), a collection of numerous connected cerebral cardiovascular conditions, is a common and growing public health problem associated with many chronic diseases worldwide. MetS components include central/abdominal obesity, systemic hypertension, diabetes, and atherogenic dyslipidemia. MetS and PD share multiple pathophysiological processes, including insulin resistance, oxidative stress, and chronic inflammation. In recent years, MetS has been linked to an increased risk of PD, according to studies; however, the specific mechanism remains unclear. Researchers also found that some related metabolic therapies are potential therapeutic strategies to prevent and improve PD. This article reviews the epidemiological relationship between components of MetS and the risk of PD and discusses the potentially relevant mechanisms and recent progress of MetS as a risk factor for PD. Furthermore, we conclude that MetS-related therapies are beneficial for the prevention and treatment of PD.

Update on the application of mesenchymal stem cell-derived exosomes in the treatment of Parkinson's disease: A systematic review.

Parkinson's disease (PD) has become the second largest neurodegenerative disease after Alzheimer's disease, and its incidence is increasing year by year. Traditional dopamine replacement therapy and deep brain stimulation can only alleviate the clinical symptoms of patients with PD but cannot cure the disease. In recent years, stem cell therapy has been used to treat neurodegenerative diseases. Many studies have shown that stem cell transplantation has a therapeutic effect on PD. Here, we review recent studies indicating that exosomes derived from mesenchymal stem cells also have the potential to treat PD in animal models, but the exact mechanism remains unclear. This article reviews the mechanisms through which exosomes are involved in intercellular information exchange, promote neuroprotection and freely cross the blood-brain barrier in the treatment of PD. The increase in the incidence of PD and the decline in the quality of life of patients with advanced PD have placed a heavy burden on patients, families and society. Therefore, innovative therapies for PD are urgently needed. Herein, we discuss the mechanisms underlying the effects of exosomes in PD, to provide new insights into the treatment of PD. The main purpose of this article is to explore the therapeutic potential of exosomes derived from mesenchymal stem cells and future research directions for this degenerative disease.

[Genetic Analysis and Prenatal Diagnosis of Thalassemia in Couples of Childbearing Age in Quanzhou Region Fujian Province, China].

OBJECTIVE: To explore the genotypes and prenatal diagnosis of thalassemia in couples of childbearing age in Quanzhou, Fujian Province. METHODS: Blood routine and hemoglobin electrophoresis were performed for initial thalassemia screening in 76 328 couples in Quanzhou region from July 2017 to July 2020. The couples with positive initial screening results further underwent thalassemia gene test. Couples carrying homotypic thalassemia genes underwent prenatal diagnosis in the second trimester. RESULTS: Among 76 328 couples of childbearing age, 1 809 couples of positive initial thalassemia screening were identified, with the positive rate about 2.37%. Further results of genetic detection of the 1 809 couples showed that 985 cases were diagnosed as α- thalassemia, of which --sea/αα was the most frequency, followed by -α3.7/αα and ααQS/αα; 296 cases were diagnosed as ß-thalassemia, the most frequency mutations were 654M/N and 41-42M/N; 26 cases of compound α and ß-thalassemia were detected. In addition, 3 rare cases of thalassemia were detected, including --THAI/αα, SEA-HPFH, and -α6.9/--sea. Among them, 108 couples were confirmed as homologous thalassemia, with the detection rate about 5.97%, including 96 couples of homologous α-thalassemia, 9 couples of homologous ß-thalassemia, and 3 couples with one had compound α- and ß-thalassemia. Among them, 17 couples with homologous α-thalassemia underwent prenatal diagnosis in the second trimester, of which 1 case of Hb Bart's Hydrops Syndrome, 3 cases of HbH disease, 9 cases of silent thalassemia or α-thalassemia minor, and 4 cases of healthy fetuses were detected. Fetal chromosome karyotype analysis showed that 16 cases were normal and 1 case diagnosed as Down syndrome. CONCLUSION: Thalassemia screening in pre-marital and pre-pregnancy, and prenatal diagnosis can effectively reduce the birth of children with thalassemia intermediate and thalassemia major. It is necessary to perform chromosome karyotype analysis at the same time as prenatal diagnosis of thalassemia gene in order to avoid fetus with abnormal chromosome.

[Genetic Testing for Alpha and Beta Thalassemia in Children in Quanzhou Region of Fujian Province in China].

OBJECTIVE: To analyze the genotypes and distribution of thalassemia in children in Quanzhou Region so as to provide reference for the prevention and control of thalassemia. METHODS: A total of 1 302 children with suspected thalassemia were collected from January 2014 to April 2020 in Quanzhou Region. The deletional α-thalassemia was detected by Gap-PCR, and DNA reverse dot blot (RDB) hybridization was used to detect α- and ß-thalassemia mutations. RESULTS: In the 1 302 cases, 667 cases were identified as thalassemia carriers, and the positive detection rate was about 51.23%. Among them, 380 cases of α-thalassemia gene were detected, and --SEA/αα was the most common genotype with the composition rate about 69.21%. Forty-two cases were identified as HbH disease, and -α3.7/--SEA was the most common genotype. While, 274 cases were identified as ß-thalassemia, and ßIVS-Ⅱ-654/ßN (35.40%) and ßCD41-42/ßN (33.94%) were the most common genotypes. Seventeen cases of ß-thalassemia major/intermedia were identified, and the most common genotypes were ßIVS-Ⅱ-654/ßIVS-Ⅱ-654 and ßIVS-Ⅱ-654/ßCD17. Meanwhile, 13 cases of α- complex ß- thalassemia were detected. Among them, 1 case of ß-thalassemia gene rare mutation Term CD+32 was firstly detected in Fujian Province, and 1 case of CD14-15 mutation was firstly detected in Quanzhou Region. In addition, 3 cases of abnormal hemoglobin disease were identified, in which 2 cases were Hb Q-Thailand and 1 case was Hb G-Honolulu. CONCLUSION: There are various genotypes of thalassemia in children in Quanzhou Region, and many children with thalassemia major or intermedia. Therefore, further prevention and control of thalassemia need to be strengthened for reducing the birth of thalassemia major or intermedia.

[Generation and characterization of the adult neuron-specific ADAM10 knock-out mice].

A disintegrin and metalloproteinase 10 (ADAM10) is a major sheddase for over 30 different membrane proteins and gets involved in such physiological processes and pathogenesis as embryonic development, cell adhesion, signal transduction, immune reaction, cancer, and Alzheimer's disease. Both ADAM10 knock-out mice and the neural progenitor cell-specific ADAM10 knock-out mice having been reported so far died in the embryonic or perinatal stage, respectively, thus resulting in the failure to investigate ADAM10 function in the adult mouse brain. Through a series of tests, we have succeeded in generating and characterizing the CaMKIIα-Cre/ADAM10(loxP/loxP) mice surviving until adulthood by means of crossing ADAM10(loxP/loxP) mice with newly generated CaMKIIα-Cre transgenic mice. PCR analysis of genomic DNAs from different regions of the ADAM10 cKO mouse brain shows that the deleted ADAM10 alleles are mainly found in the cortex and hippocampus. Real-time RT-PCR findings further confirm that ADAM10 mRNAs decrease in the cortex and hippocampus by 55.7% and 60.8%, respectively. Western-blotting analysis demonstrates 63% and 84.8% loss of mature ADAM10 proteins from the cortex and hippocampus. Immunohistochemical tests show that there is significantly less ADAM10- positive staining in the cortical and hippocampal neurons but not gliocytes of ADAM10 cKO mice compared with control mice. In summary, we established the adult neuron-specific ADAM10 knock-out (cKO) mice for the first time, which prevented ADAM10(-/-) mice from the embryonic and perinatal mortality and laid a firm foundation for the further study of ADAM10 function in the brain of adult mice in vivo.