scholarly journals Decreased kinesin-1 mitigates NMDA-induced exicitotoxicity and ischemia-evoked neurodegeneration

2018 ◽  
Author(s):  
Raozhou Lin ◽  
Zhigang Duan ◽  
Haitao Sun ◽  
Man-Lung Fung ◽  
Hansen Chen ◽  
...  
Keyword(s):  
Heavy Chain ◽  
Neural Activity ◽  
Neurodegenerative Disorders ◽  
Therapeutic Target ◽  
Molecular Mechanisms ◽  
Potential Therapeutic Target ◽  
Aspartate Receptor ◽  
Cytoplasmic Tails ◽  
Direct Binding ◽  
Activity Dependent

AbstractN-methyl-D-aspartate receptor (NMDAR) is highly compartmentalized in neurons and the dysfunction has been implicated in various neuropsychiatric and neurodegenerative disorders. Recent failure to exploit NMDAR antagonization as a potential therapeutic target has driven the need to identify molecular mechanisms that regulate NMDAR compartmentalization. Here, we report that neural activity-dependent reduction of Kif5b, the heavy chain of kinesin-1, protected neurons against NMDA-induced excitotoxicity and ischemia-provoked neurodegeneration. Direct binding of Kinesin-1 to the GluN2B cytoplasmic tails regulated levels of NMDAR at extrasynaptic sites and the subsequent influx of calcium mediated by extrasynaptic NMDAR via regulating the insertion of NMDARs into neuronal surface. Transient increase of Kif5b restored the surface levels of NMDAR and the decreased neuronal susceptibility to NMDA-induced excitotoxicity. Our findings reveal that kinesin-1 regulates extrasynaptic NMDAR targeting and signaling, and the reduction of kinesin-1 could be regulated by neural activity and could be exploited to postpone or halt neurodegeneration.

Evaluation of MACF1-regulatory non-coding RNA as a potential therapeutic target in Colorectal Cancer

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Rowaida Mohammed Reda M. M Aboushahba ◽  
Fayda Ibrahim Abdel Motaleb ◽  
Ahmed Abdel Aziz Abou-Zeid ◽  
Enas Samir Nabil ◽  
Dalia Abdel-Wahab Mohamed ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Wnt Signaling ◽  
Cell Line ◽  
Signaling Pathway ◽  
Therapeutic Target ◽  
Molecular Mechanisms ◽  
Wnt Signaling Pathway ◽  
Control Group ◽  
Potential Therapeutic Target

ABSTRACT Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths world-wide. There is an increasing need for the identification of novel biomarkers/targets for early diagnosis and for the development of novel chemopreventive and therapeutic agents for CRC. Recently, MACF1 gene has emerged as a potential therapeutic target in cancer as it involved in processes critical for tumor cell proliferation, invasion and metastasis. It is suggested that MACF1 may function in cancers through Wnt signaling. MiR-34a is a well-known tumor suppressor miRNA.miR-34a targets MACF1 gene as a part of the wnt signaling pathway. In this study, 40 colonic tissues were collected from CRC patients (20) and control subjects (20). miR-34a-5p was assessed by real time PCR in all study groups. The results showed highly significant decrease (P < 0.01) in miR-34a relative expression in the CRC group (median RQ 0.13) when compared to the benign group (median RQ 5.3) and the healthy control group (median RQ 19.63). miR-34a mimic and inhibitor were transfected in CaCo-2 cell line and proliferation was assessed. The transfection of the cell line with miR-34a mimic decreased cell proliferation. Our study suggests that miR-34a-5p targets MACF1 gene as a part of the wnt signaling pathway leading to the involvement in the molecular mechanisms of CRC development and progression.

scholarly journals Molecular Mechanisms of Glial Cells Related Signaling Pathways Involved in the Neuroinflammatory Response of Depression

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Junhui Wang ◽  
Jie Qin ◽  
Peng Wang ◽  
Yu Sun ◽  
Qi Zhang
Keyword(s):  
Psychiatric Disorders ◽  
Signaling Pathways ◽  
Glial Cells ◽  
Therapeutic Target ◽  
Molecular Mechanisms ◽  
Pathological Change ◽  
Basic Knowledge ◽  
Pathological Features ◽  
Potential Therapeutic Target ◽  
Neuroinflammatory Response

Dysfunction of the glial cells, such as astrocytes and microglia, is one of the pathological features in many psychiatric disorders, including depression, which emphasizes that glial cells driving neuroinflammation is not only an important pathological change in depression but also a potential therapeutic target. In this review, we summarized a recent update about several signaling pathways in which glial cells may play their roles in depression through neuroinflammatory reactions. We focused on the basic knowledge of these signaling pathways by elaborating each of them. This review may provide an updated image about the recent advances on these signaling pathways that are essential parts of neuroinflammation involved in depression.

scholarly journals Selective autophagy as a potential therapeutic target for neurodegenerative disorders

2018 ◽  
Vol 17 (9) ◽  
pp. 802-815 ◽  
Author(s):  
Aurora Scrivo ◽  
Mathieu Bourdenx ◽  
Olatz Pampliega ◽  
Ana Maria Cuervo
Keyword(s):  
Neurodegenerative Disorders ◽  
Therapeutic Target ◽  
Potential Therapeutic Target ◽  
Selective Autophagy

IRAK4 Inhibition Attenuates Interleukin‐1‐Induced Astrogliosis: A Potential Therapeutic Target for Neurodegenerative Disorders?

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Evan L. Reeder ◽  
Sean M. Collins ◽  
Poornima Gopalan ◽  
Sophia V. Norman ◽  
Christopher J. O'Connell ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Therapeutic Target ◽  
Interleukin 1 ◽  
Potential Therapeutic Target

scholarly journals Seasonal regulation of singing-driven gene expression associated with song plasticity in the canary, an open-ended vocal learner

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Shin Hayase ◽  
Chengru Shao ◽  
Masahiko Kobayashi ◽  
Chihiro Mori ◽  
Wan-chun Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Neural Activity ◽  
Molecular Mechanisms ◽  
Vocal Learning ◽  
Motor Nucleus ◽  
Vocal Plasticity ◽  
Learning Capacity ◽  
Induction Rate ◽  
Song Acquisition ◽  
Activity Dependent

AbstractSongbirds are one of the few animal taxa that possess vocal learning abilities. Different species of songbirds exhibit species-specific learning programs during song acquisition. Songbirds with open-ended vocal learning capacity, such as the canary, modify their songs during adulthood. Nevertheless, the neural molecular mechanisms underlying open-ended vocal learning are not fully understood. We investigated the singing-driven expression of neural activity-dependent genes (Arc, Egr1, c-fos, Nr4a1, Sik1, Dusp6, and Gadd45β) in the canary to examine a potential relationship between the gene expression level and the degree of seasonal vocal plasticity at different ages. The expression of these genes was differently regulated throughout the critical period of vocal learning in the zebra finch, a closed-ended song learner. In the canary, the neural activity-dependent genes were induced by singing in the song nuclei throughout the year. However, in the vocal motor nucleus, the robust nucleus of the arcopallium (RA), all genes were regulated with a higher induction rate by singing in the fall than in the spring. The singing-driven expression of these genes showed a similar induction rate in the fall between the first year juvenile and the second year adult canaries, suggesting a seasonal, not age-dependent, regulation of the neural activity-dependent genes. By measuring seasonal vocal plasticity and singing-driven gene expression, we found that in RA, the induction intensity of the neural activity-dependent genes was correlated with the state of vocal plasticity. These results demonstrate a correlation between vocal plasticity and the singing-driven expression of neural activity-dependent genes in RA through song development, regardless of whether a songbird species possesses an open- or closed-ended vocal learning capacity.

scholarly journals MicroRNA-204-5p Inhibits Ovarian Cancer Cell Proliferation by Down-Regulating USP47

2019 ◽  
Vol 28 (1_suppl) ◽  
pp. 51S-58S ◽  
Author(s):  
Liangliang Hu ◽  
Helena Kolibaba ◽  
Siyou Zhang ◽  
Minhua Cao ◽  
Huihui Niu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Therapeutic Target ◽  
Molecular Mechanisms ◽  
Ovarian Cancer Cell ◽  
Malignant Tumors ◽  
Gynecologic Cancer ◽  
Cancer Cell Proliferation ◽  
Potential Therapeutic Target ◽  
Human Malignant Tumors

Ovarian cancer (OC) is the most lethal gynecologic cancer, and the incidence of OC has risen steadily worldwide. Numerous microRNAs (miRNAs) have been found to be involved in the progression of OC. miR-204-5p is down-regulated and functions as a tumor suppressor in various types of human malignant tumors. However, the biological roles and molecular mechanisms of miR-204-5p in OC still remain unclear. In this study, the aberrant down-regulation of miR-204-5p was detected in OC tissues. We also observed that miR-204-5p overexpression represses OC cell proliferation. Ubiquitin-specific peptidase 47 (USP47) is verified as the functional target of miR-204-5p, through which it plays an important biological role in OC. Our results uncover new functions and mechanisms for miR-204-5p in the progression of OC, and provide a potential therapeutic target for the treatment of OC.

The regulatory role of Rho GTPases and their substrates in osteoclastogenesis

2020 ◽  
Vol 21 ◽  
Author(s):  
Lin Gao ◽  
Lingbo Kong ◽  
Yuanting Zhao
Keyword(s):  
Bone Loss ◽  
Therapeutic Target ◽  
Rho Gtpases ◽  
Molecular Mechanisms ◽  
Special Role ◽  
Cellular Functions ◽  
Potential Therapeutic Target ◽  
Cytoskeletal Organization ◽  
Osteoclastic Differentiation

: Pathological bone loss diseases (osteolysis, Paget’s diseases) are commonly caused by the over differentiation and activity of osteoclasts. The Rho GTPases family members Rac1/2 (Rac1 and Rac2) have been reported for their special role in exerting multiple cellular functions during osteoclastic differentiation, which including the most prominent function on dynamic actin cytoskeleton rearranging. Besides that, the increasing studies demonstrated the regulating effects of Rac1/2 on osteoclastic cytoskeletal organization is through the GEFs member Dock5. Although the amount of relevant studies on this topic still limited, there are several excellent studies have been reported for extensively explored the molecular mechanisms involved in Rac1/2 and Dock5 during the osteoclastogenesis regulation, as well as their role as the therapeutic target in bone loss disesases. Herein in this review, we aim to focus on recent advances studies for extensively understanding the role of Rho GTPases Rac1/2 and Dock5 in osteoclastogenesis, as well as their role as a potential therapeutic target in regulating osteoclastogenesis.

scholarly journals Ghrelin is neuroprotective in Parkinson’s disease: molecular mechanisms of metabolic neuroprotection

2013 ◽  
Vol 4 (1) ◽  
pp. 25-36 ◽  
Author(s):  
Jacqueline A. Bayliss ◽  
Zane B. Andrews
Keyword(s):  
Reactive Oxygen Species ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Function ◽  
Therapeutic Target ◽  
Molecular Mechanisms ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Potential Therapeutic Target ◽  
Neuroprotective Effects

Ghrelin is a circulating orexigenic signal that rises with prolonged fasting and falls postprandially. Ghrelin regulates energy homeostasis by stimulating appetite and body weight; however, it also has many nonmetabolic functions including enhanced learning and memory, anxiolytic effects as well as being neuroprotective. In Parkinson’s disease, ghrelin enhances dopaminergic survival via reduced microglial and caspase activation and improved mitochondrial function. As mitochondrial dysfunction contributes to Parkinson’s disease, any agent that enhances mitochondrial function could be a potential therapeutic target. We propose that ghrelin provides neuroprotective effects via AMPK (5′ adenosine monophosphate-activated protein kinase) activation and enhanced mitophagy (removal of damaged mitochondria) to ultimately enhance mitochondrial bioenergetics. AMPK activation shifts energy balance from a negative to a neutral state and has a role in regulating mitochondrial biogenesis and reducing reactive oxygen species production. Mitophagy is important in Parkinson’s disease because damaged mitochondria produce reactive oxygen species resulting in damage to intracellular proteins, lipids and DNA predisposing them to neurodegeneration. Many genetic mutations linked to Parkinson’s disease are due to abnormal mitochondrial function and mitophagy, for example LRRK2, PINK1 and Parkin. An interaction between ghrelin and these classic Parkinson’s disease markers has not been observed, however by enhancing mitochondrial function, ghrelin or AMPK is a potential therapeutic target for slowing the progression of Parkinson’s disease symptoms, both motor and nonmotor.

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