Aberrant Activation of Cdc2/cyclin B1 Is Involved in Initiation of Cytoskeletal Pathology in Murine Niemann-Pick Disease Type C / 华中科技大学学报（医学）（英德文版）

Niemann-Pick disease type C (NPC) is a fatal,neurovisceral lipid storage disease,neuropathologically characterized by cytoplasmic sequestration of glycolipids in neurons,progressive neuronal loss,neurofibrillary tangles (NFTs) formation,and axonal spheroids (AS).Cytoskeletal pathology including accumulation of hyperphosphorylated cytoskeletal proteins is a neuropathological hallmark of the mouse model of NPC (npc mice).With a goal of elucidating the mechanisms underlying the lesion formation,we investigated the temporal and spatial characteristics of cytoskeletal lesions and the roles of cdc2,cdk4,and cdk5 in lesion formation in young npc mice.Cytoskeletal lesions were detectable in npc mice at three weeks of age.Importantly,concomitant activation of cdc2/cyclin B 1 kinase and accumulation of a subsequently generated cohort of phospho-epitopes were detected.The activation of cdk4/cyclin D1 and cdk5/p25 kinases was observed during the fourth week of life in npc mice,and this activation contributed to the lesion formation.We concluded that the progression of cytoskeletal pathology in npc mice older than four weeks is accelerated by the cumulative effect of cdc2,cdk4,and cdk5 activation.Furthermore,cdc2/cyclin B1 may act as a key initial player one week earlier.Targeting cell cycle activation may be beneficial to slow down the NPC pathogenesis.

Intracranial Hypertension Syndrome in Systemic Lupus Erythema-tosus:Clinical Analysis and Review of the Literature / 华中科技大学学报（医学）（英德文版）

In order to better understand the clinical manifestation of systemic lupus erythematosus (SLE) with intracranial hypertension syndrome (IHS),we analyzed the clinical features and treatment of a typical SLE patient with IHS.SLE is one of the most unpredictable autoimmune diseases in-volving multiple organ systems that is defined clinically and associated with antibodies directed against cell nuclei.IHS is an uncommon manifestation of neuropsychiatric SLE (NPSLE) and is characterized by an elevated intracranial pressure,papilledema,and headache with occasional ab-ducens nerve paresis,absence of a space-occupying lesion or ventricular enlargement,and normal cerebrospinal fluid chemical and hematological constituents.IHS has been reported in a few sporadic cases in patients with SLE worldwide,but rarely has been reported in China.In this study,a 34-year-old female SLE patient with IHS was.reported and pertinent literature reviewed.The clinical presentation,image logical features,and investigatory findings were discussed.

Packaging and Functional Identification of Recombinant A deno-associated Virus Encoding cdc2-siRNA / 华中科技大学学报（医学）（英德文版）

Cyclin dependent kinases (cdks) play an important role in the pathogenesis of multiple neurodegenerative diseases. To explore the possibility of cdks-related gene therapy for neurodegenerative diseases, we packed recombinant adeno-associated virus (rAAV) encoding cdc2-siRNA. The expressing plasmid pAAV-MCS-EGFP-U6-odc2-siRNA was constructed by using molecular biological techniques. The rAAV encoding cdc2-siRNA (rAAV-EGFP-U6-cdc2-siRNA) was packed by calcium phosphate mediated co-transfection of the plasmid pAAV-MCS-EGFP-U6-cdc2-siRNA, p-RC and p-Helper into AAV-293 cells. DNA sequencing proved the successful construction of U6-cdc2-siRNA in pAAV-MCS-EGFP. Seventy-two h after packaging, the expression of EGFP could be detected in AAV-293 cells. Western blotting revealed that cdc2 gene expression in AAV-293 cells was down-regulated markedly after transfection with rAAV-EGFP-U6-cdc2-siRNA, which evidenced the satisfactory silencing effect of this virus. It was concluded that the packaging of rAAV encoding cdc2-siRNA was successful, rAAV encoding cdc2-siRNA could silence cdc2 gene effectively, which might offer a novel means for the treatment of neurodegenerative diseases.