Modulator of apoptosis protein1 (MOAP1), also known as MAP1 and PNMA4, belongs to the PNMA gene family consisting of at least 15 genes located on different chromosomes. MOAP1 interacts with the BAX protein, one of the most important apoptosis regulators. Due to its critical role in a few of disease-associated pathways, MOAP1 is associated with many diseases such as cancers and neurological diseases. In this study, we introduced MOAP1 and its biological functions and reviewed the associations between MOAP1 and a few diseases including cancers, neurological diseases, and other diseases such as inflammation and heart diseases. We also explained possible biological mechanisms underlying the associations between MOAP1 and these diseases, and discussed a few future directions regarding MOAP1, especially its potential roles in neurodegenerative disorders. In summary, MOAP1 plays a critical role in the development and progression of cancers and neurological diseases by regulating a few genes related to cellular apoptosis such as BAX and RASSF1A and interacting with disease-associated miRNAs, including miR-25 and miR1228.
Mitotic arrest deficient 2-like protein 2 (MAD2B) is not only a DNA damage repair agent but also a cell cycle regulator that is widely expressed in the hippocampus and the cerebral cortex. However, the functions of MAD2B in hippocampal and cerebral cortical neurons are poorly understood. In this study, we crossed MAD2Bflox/flox and calcium/calmodulin-dependent protein kinase II alpha (Camk2a)-Cre mice to conditionally knock out MAD2B in the forebrain pyramidal neurons by the Cre/loxP recombinase system. First, RNA sequencing suggested that the differentially expressed genes in the hippocampus and the cerebral cortex between the WT and the MAD2B cKO mice were related to learning and memory. Then, the results of behavioral tests, including the Morris water maze test, the novel object recognition test, and the contextual fear conditioning experiment, suggested that the learning and memory abilities of the MAD2B cKO mice had improved. Moreover, conditional knockout of MAD2B increased the number of neurons without affecting the number of glial cells in the hippocampal CA1 and the cerebral cortex. At the same time, the number of doublecortin-positive (DCX+) cells was increased in the dentate gyrus (DG) of the MAD2B cKO mice. In addition, as shown by Golgi staining, the MAD2B cKO mice had more mushroom-like and long-like spines than the WT mice. Transmission electron microscopy (TEM) revealed that spine synapses increased and shaft synapses decreased in the CA1 of the MAD2B cKO mice. Taken together, our findings indicated that MAD2B plays an essential role in regulating learning and memory.
Background Depression is a prevalent and recurrent psychiatric disorder. Aberrant neural structure and activity play fundamental roles in the occurrence of depression. Mitotic arrest deficient protein (MAD2B) is highly expressed in neurons and may be implicated in synaptic plasticity in the central nervous system. However, the effect of MAD2B in depression, as well as the related molecular mechanism, is uncertain. Methods Here, we employed mouse models of depression induced by chronic unpredictable stress (CUS) exposure or corticosterone (CORT) stimulation. Depression-like behaviors in mice were evaluated by sucrose preference, forced swimming, and tail suspension tests. Hippocampal MAD2B overexpression was mediated by adeno-associated virus 8 containing eGFP. In vitro, primary neuronal cells were obtained from the hippocampus of rat embryos and were treated with CORT; while MAD2B overexpression was performed using lentivirus. MAD2B and glutamate metabotropic receptor 4 (GRM4) levels were evaluated by Western blots and qPCR. Primary neuronal miR-29b-3p expression was detected by qPCR. Results MAD2B expression was reduced in the hippocampus in mice exhibiting depressive-like behaviors. However, hippocampal MAD2B overexpression protected mice from developing either CUS- or CORT-induced depression-like behaviors, an effect associated with reduced expression of GRM4, a presynaptic receptor involved in depression. Moreover, MAD2B overexpression in primary neuronal cells also decreased GRM4 expression while enhancing the level of miR-29b-3p; this phenomenon was also observed under CORT stimulation. Conclusions Our results suggest an important role of neuronal MAD2B in the pathogenesis of depression via the miR-29b-3p/ GRM4 signaling pathway. MAD2B could be a potential therapeutic target for depressive disorders.
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