Down‐regulation of MET in hippocampal neurons of Alzheimer's disease brains

Abstract

We found that mRNA of MET, the receptor of hepatocyte growth factor (HGF), is significantly decreased in the hippocampus of Alzheimer's disease (AD) patients. Therefore, we tried to determine the cellular component-dependent changes of MET expressions. In this study, we examined cellular distribution of MET in the cerebral neocortices and hippocampi of 12 AD and 11 normal controls without brain diseases. In normal brains, MET immunoreactivity was observed in the neuronal perikarya and a subpopulation of astrocytes mainly in the subpial layer and white matter. In AD brains, we found marked decline of MET in hippocampal pyramidal neurons and granule cells of dentate gyrus. The decline was more obvious in the pyramidal neurons of the hippocampi than that in the neocortical neurons. In addition, we found strong MET immunostaining in reactive astrocytes, including those near senile plaques. Given the neurotrophic effects of the HGF/MET pathway, this decline may adversely affect neuronal survival in AD cases. Because it has been reported that HGF is also up-regulated around senile plaques, β-amyloid deposition might be associated with astrocytosis through the HGF signaling pathway.

MicroRNA‑449a regulates the progression of brain aging by targeting SCN2B in SAMP8 mice

“…HGF/MET was able to induce dendritic arborization and synaptogenesis when stimulated by N-hexanoic-Tyr-Ile-(6) aminohexanoic amide and it served a role in facilitating the formation of new functional synaptic connections and augmenting memory consolidation in animal models of Ad (58). The downregulation of HGF/MET in the brain functional regions of patients with Ad was associated with a poor prognosis (59). Syt1, as a novel amyloid precursor protein-interacting protein, promotes Aβ generation and regulates the Aβ level of the synapse, serving a potentially important role in the pathogenesis of AD (60,61).…”

HGF Mediates Clinical‐Grade Human Umbilical Cord‐Derived Mesenchymal Stem Cells Improved Functional Recovery in a Senescence‐Accelerated Mouse Model of Alzheimer's Disease

“…We focused on secretory factors expressing the strongest signal (Figure 4B), and combined this with bioinformatics analysis and literature search to analyze the role of each factor in detail (data not shown); we then selected four potential factors including IL‐6, HGF, ANG, and sgp130, which may be involved in damage repair. [ 42–46 ] With the mature and stable OA‐induced damage model in vitro, several key indexes were investigated to analyze and compare the repair features of the four factors. We observed that only HGF substantially ameliorated neural cell damage (Figure S5, Supporting Information) in multiple ways, including dendritic length and mitochondrial function.…”

Associations of the cerebrospinal fluid hepatocyte growth factor with Alzheimer’s disease pathology and cognitive function

“…HGF-cMet signaling induces cell proliferation, glucose metabolism, neuroregeneration, and neuroprotection [ 34 – 36 ]. Hamasaki et al’ study indicated that the cMet level was decreased in granule cells of the dentate gyrus and hippocampal pyramidal neurons in AD brains [ 37 ]. In particular, cMet in hippocampal pyramidal neurons decreased more significantly than in neocortical neurons [ 37 ].…”