中枢神经系统的神经生长因子的代谢途径及唐氏综合症和阿尔茨海默病的调节异常

Title:The NGF Metabolic Pathway in the CNS and its Dysregulation in Down Syndrome and Alzheimer’s Disease

Volume: 13 Issue: 1

Author(s): M. Florencia Iulita and A. Claudio Cuello

Affiliation:

关键词: Alzheimer's disease

摘要: It is well established that individuals with Down syndrome develop Alzheimer’s disease neuropathology by middle age. Both in Alzheimer’s disease and Down syndrome, this is accompanied by the atrophy of NGF-dependent cholinergic neurons of the basal forebrain. An NGF trophic compromise in Alzheimer’s disease had been early suspected. This hypothesis was discarded with the finding of unaltered NGF mRNA synthesis and of increased NGF precursor levels (proNGF) in postmortem Alzheimer’s disease brains. The possibility of an NGF trophic disconnection has been recently revisited at the light of a newly discovered extracellular NGF metabolic pathway; where proNGF is released in an activity-dependent manner and converted by plasmin to mature NGF in the extracellular space. Mature NGF is ultimately degraded by the metalloprotease MMP-9. This pathway has been shown to be compromised in Alzheimer’s disease and Down syndrome brains, thus reviving the trophic factor hypothesis to explain the atrophy of basal forebrain cholinergic neurons in these disorders. This chapter will discuss the physiological role of NGF and its biological significance to cholinergic neurons of the CNS, and present the evidence for a dysregulation of the NGF metabolism in Alzheimer’s disease and Down syndrome.

Cite this article as:

M. Florencia Iulita and A. Claudio Cuello , The NGF Metabolic Pathway in the CNS and its Dysregulation in Down Syndrome and Alzheimer’s Disease, Current Alzheimer Research 2016; 13 (1) . https://dx.doi.org/10.2174/1567205012666150921100030