GRK5 Deficiency Leads to Selective Basal Forebrain Cholinergic Neuronal Vulnerability.
GRK5 Deficiency Leads to Selective Basal Forebrain Cholinergic Neuronal Vulnerability.
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DOI：
10.1038/srep26116
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发表时间：
2016-05-19
影响因子：
4.6
通讯作者：
Suo WZ
中科院分区：
文献类型：
--
作者：
He M;Singh P;Cheng S;Zhang Q;Peng W;Ding X;Li L;Liu J;Premont RT;Morgan D;Burns JM;Swerdlow RH;Suo WZ
Why certain diseases primarily affect one specific neuronal subtype rather than another is a puzzle whose solution underlies the development of specific therapies. Selective basal forebrain cholinergic (BFC) neurodegeneration participates in cognitive impairment in Alzheimer’s disease (AD), yet the underlying mechanism remains elusive. Here, we report the first recapitulation of the selective BFC neuronal loss that is typical of human AD in a mouse model termed GAP. We created GAP mice by crossing Tg2576 mice that over-express the Swedish mutant human β-amyloid precursor protein gene with G protein-coupled receptor kinase-5 (GRK5) knockout mice. This doubly defective mouse displayed significant BFC neuronal loss at 18 months of age, which was not observed in either of the singly defective parent strains or in the wild type. Along with other supporting evidence, we propose that GRK5 deficiency selectively renders BFC neurons more vulnerable to degeneration.
