From neurodevelopment to neurodegeneration: the interaction of neurofibromin and valosin-containing protein/p97 in regulation of dendritic spine formation

Journal of Biomedical Science

Yi-Ping Hsueh¹ 

[1] Institute of Molecular Biology, Academia Sinica, 128, Sec 2, Academia Rd, Taipei 11529, Taiwan

关键词: VCP/p97.;    statin;    neurofibromin;    Neurofibromatosis Type I;    Neurodevelopmental disorder;    IBMPFD;    Dendritic spine formation;   

Others  :  825396
DOI  :  10.1186/1423-0127-19-33

 received in 2012-03-03, accepted in 2012-03-26,  发布年份 2012

【 摘 要 】

Both Neurofibromatosis type I (NF1) and inclusion body myopathy with Paget's disease of bone and frontotemporal dementia (IBMPFD) are autosomal dominant genetic disorders. These two diseases are fully penetrant but with high heterogeneity in phenotypes, suggesting the involvement of genetic modifiers in modulating patients' phenotypes. Although NF1 is recognized as a developmental disorder and IBMPFD is associated with degeneration of multiple tissues, a recent study discovered the direct protein interaction between neurofibromin, the protein product of the NF1 gene, and VCP/p97, encoded by the causative gene of IBMPFD. Both NF1 and VCP/p97 are critical for dendritic spine formation, which provides the cellular mechanism explaining the cognitive deficits and dementia found in patients. Moreover, disruption of the interaction between neurofibromin and VCP impairs dendritic spinogenesis. Neurofibromin likely influences multiple downstream pathways to control dendritic spinogenesis. One is to activate the protein kinase A pathway to initiate dendritic spine formation; another is to regulate the synaptic distribution of VCP and control the activity of VCP in dendritic spinogenesis. Since neurofibromin and VCP/p97 also regulate cell growth and bone metabolism, the understanding of neurofibromin and VCP/p97 in neurons may be applied to study of cancer and bone. Statin treatment rescues the spine defects caused by VCP deficiency, suggesting the potential role of statin in clinical treatment for these two diseases.

【 授权许可】

   
2012 Hsueh; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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