ABSTRACT
Imbalance of calcium homeostasis and abnormal autophagy are important pathogenesis mechanisms for neurodegenerative diseases, as PD, AD, and amyotrophic lateral sclerosis (ALS); and correlation is noted between imbalance of calcium homeostasis and abnormal autophagy. A number of studies have reported that different calcium storage compartments of cells can affect autophagy via calcium channels or Ca 2+-related signal proteins, such as cytoplasm calcium release-activated calcium modulator 1 (Orai1) and transient receptor potential canonical channel (TRPC), endoplasmic reticulum calcium channel inositol 1,4,5-triphosphate receptor (IP3R), mitochondrial calcium uniporter (MCU) related to Ca 2+ uptake, lysosomal calcium channel transient receptor potential channel mucolipin 1(TRPML1) and two-pore channels, cytoplasmic Ca 2+/calmodulin-dependent kinase kinase β (CaMKKβ)/AMP-activated protein kinase(AMPK) pathway. This review summarizes the research progress on autophagy regulated by Ca 2+ in intracellular calcium storage compartments and cytoplasm in neurodegenerative diseases, with a view to further understand the pathogenesis of these diseases.
ABSTRACT
Parkinson's disease is the second most common neurodegeneration, and its pathogenesis is related to mitochondrial dysfunction, oxidative stress and calcium homeostasis imbalance. In recent years, the relationship between Parkinson's disease and Ca 2+ has become a research hotspot. Calcium homeostasis disorders can lead to Parkinson's disease in different ways. The level of intracellular calcium ion depends on store-operated calcium entry (SOCE), calcium release-activated calcium modulator1 (Orai1), stromal interaction molecule 1 (STIM1) and transient receptor potential channel 1 (TRPC1) can form a functional complex to regulate it. PD neurotoxins can selectively damage dopaminergic neurons by reducing the function of Orai1-STIM1-TRPC1 complex and damaging SOCE and its downstream signal pathways. And the complex may affect the development of Parkinson's disease by acting on microglia and endoplasmic reticulum stress, and then regulate neuroinflammation and autophagy. Therefore, restoring the expression and function of Orai1-STIM1-TRPC1 function complex and maintaining calcium homeostasis may be the therapeutic targets of Parkinson's disease.
ABSTRACT
Anaplastic large cell lymphoma (ALCL) is a clinically rare non-Hodgkin's lymphoma which is characterized by malignant "hallmark cells" and strong expression of CD30 in membrane and golgi patterns in almost all cases. The most frequent chromosomal translocation is t (2;5)(p23;q35). ALCL in children is nearly universally anaplastic lymphoma kinase (ALK) positive and commonly present with advanced systemic disease. Many different treatment strategies have been utilized with similar event free survival rates of 65%~75%. High-risk and recurrent/refractory ALCL can be treated by vinblastine weekly or hematopoietic stem cell transplantation. Novel therapies such as CD30 targeted treatment and ALK inhibitors may soon radically change the treatment paradigm for this disease. This review will provide an overview of the biological characteristics, clinical features, treatment and prognostic factors for children with ALCL.
ABSTRACT
<p><b>OBJECTIVE</b>To summarize the clinical features, imaging characteristics, diagnosis and treatment of a case with central nervous system infection caused by Exophiala dermatitidis, as well as to review the related literature.</p><p><b>METHOD</b>Associated literature and clinical data of an 8-year-old boy who was diagnosed as central nervous system infection caused by Exophiala dermatitidis in Beijing Children's Hospital Affiliated to Capital Medical University and hospitalized twice from 2012 to 2014 were analyzed retrospectively.</p><p><b>RESULT</b>The boy was 8 years old with the chief complaint of dizziness for 2 months, intermittent fever for 1 month accompanied with spasm twice. He was diagnosed as bile ducts space-occupying lesions 2 years ago, when the pathological diagnosis was fungal infection. The boy was treated with irregular anti-fungal therapy. Then the boy developed nervous symptoms, impaired consciousness and abnormal physical activity that developed gradually. After hospitalization the cerebral MRI of the boy showed space-occupying lesions accompanied with edema of surrounding area. Filamentous fungi was found by brain biopsy, which was culture positive for Exophiala dermatitidis. After diagnosis the boy was treated with amphotericin B (AMB), voriconazole and 5-Fu, as well as symptomatic treatment. The state of the boy was improved gradually. Two months later, the boy could communicate with others normally and move personally. The lesions and edema seen on the MRI was decreased moderately. Accordingly, the boy was treated with oral voriconazole maintenance treatment for about 1 year and 4 months after discharge. During this period, the state of him was stable without symptoms. The lesions shown by MRI did not disappear but decreased on regular examination. However, recently the disease of the boy progressed again, with dizziness, neck pain, headache and progressive nervous symptoms (intermittent spasm, inability to cough, and impaired consciousness). The boy died at last, even with the active treatment at the second hospitalization. Exophiala dermatitidis was culture-positive again in his CSF, and was confirmed by PCR successfully.</p><p><b>CONCLUSION</b>The central nervous system infection caused by Exophiala dermatitidis is rare. Clinical features of this disease were similar to those of other fungal CNS infection, cerebral MRI of which could show the similar lumpy lesions. Diagnosis of the disease should be based on pathology and culture.</p>