- 作者: Yi-Ping Hsueh
- 作者服務機構: Institute of Molecular Biology, Academia Sinica, Taiwan, R.O.C.
- 中文摘要: --
- 英文摘要:
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 controls
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. - 中文關鍵字: --
- 英文關鍵字: Dendritic spine formation, IBMPFD, Neurodevelopmental disorder, Neurofibromatosis Type I, neurofibromin, statin, VCP/p97.