scholarly journals The role of P53 up-regulated modulator of apoptosis (PUMA) in ovarian development, cardiovascular and neurodegenerative diseases

APOPTOSIS ◽  
2021 ◽  
Author(s):  
Mei Li
Keyword(s):  
Neurodegenerative Diseases ◽  
Ovarian Development ◽  
Critical Role ◽  
Ovary Development ◽  
Mitochondrial Apoptosis ◽  
The Past ◽  
Apoptotic Pathways ◽  
Extrinsic Apoptotic Pathways ◽  
Transcriptional Target

AbstractP53 up-regulated modulator of apoptosis (PUMA), a pro-apoptotic BCL-2 homology 3 (BH3)-only member of the BCL-2 family, is a direct transcriptional target of P53 that elicits mitochondrial apoptosis under treatment with radiation and chemotherapy. It also induces excessive apoptosis in cardiovascular and/or neurodegenerative diseases. PUMA has been found to play a critical role in ovarian apoptosis. In the present paper, we review the progress of the study in PUMA over the past two decades in terms of its inducement and/or amplification of programmed cell death and describe recent updates to the understanding of both P53-dependent and P53-independent PUMA-mediated apoptotic pathways that are implicated in physiology and pathology, including the development of the ovary and cardiovascular and neurodegenerative diseases. We propose that PUMA may be a key regulator during ovary development, provide a model for PUMA-mediated apoptotic pathways, including intrinsic and extrinsic apoptotic pathways.

scholarly journals The Critical Role of PPARγin Human Malignant Melanoma

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-5 ◽  
Author(s):  
Christian Freudlsperger ◽  
Udo Schumacher ◽  
Siegmar Reinert ◽  
Jürgen Hoffmann
Keyword(s):  
Potential Role ◽  
Critical Role ◽  
Apoptosis Resistance ◽  
Human Malignant Melanoma ◽  
The Past ◽  
Anticancer Effects ◽  
Survival Capacity ◽  
Apoptotic Pathways ◽  
Melanoma Therapy

The past 30 years have only seen slight improvement in melanoma therapy. Despite a wide variety of therapeutic options, current survival for patients with metastatic disease is only 6–8 months. Part of the reason for this treatment failure is the broad chemoresistance of melanoma, which is due to an altered survival capacity and an inactivation of apoptotic pathways. Several targetable pathways, responsible for this survival/apoptosis resistance in melanoma, have been described and current research has focused on mechanism inactivating these pathways. As PPARγwas shown to be constitutively active in several tumour entities and PPARγagonists extent strong anticancer effects, the role of PPARγas a possible target for specific anticancer strategy was investigated in numerous studies. However, only a few studies have focused on the effects of PPARγagonists in melanoma, showing conflicting results. The use of PPARγagonists in melanoma therapy has to be carefully weighted against considerable, undesirable side effects, as their mode of action is not fully understood and even pro-proliferative effects have been described. In the current review, we discuss the role of PPARs, in particular PPARγin melanoma and their potential role as a molecular target for melanoma therapy.

scholarly journals The HIF target MAFF promotes tumor invasion and metastasis through IL11 and STAT3 signaling

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Eui Jung Moon ◽  
Stephano S. Mello ◽  
Caiyun G. Li ◽  
Jen-Tsan Chi ◽  
Kaushik Thakkar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Invasion ◽  
Critical Role ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Invasion And Metastasis ◽  
Stat3 Signaling ◽  
Inducible Genes ◽  
Transcriptional Target

AbstractHypoxia plays a critical role in tumor progression including invasion and metastasis. To determine critical genes regulated by hypoxia that promote invasion and metastasis, we screen fifty hypoxia inducible genes for their effects on invasion. In this study, we identify v-maf musculoaponeurotic fibrosarcoma oncogene homolog F (MAFF) as a potent regulator of tumor invasion without affecting cell viability. MAFF expression is elevated in metastatic breast cancer patients and is specifically correlated with hypoxic tumors. Combined ChIP- and RNA-sequencing identifies IL11 as a direct transcriptional target of the heterodimer between MAFF and BACH1, which leads to activation of STAT3 signaling. Inhibition of IL11 results in similar levels of metastatic suppression as inhibition of MAFF. This study demonstrates the oncogenic role of MAFF as an activator of the IL11/STAT3 pathways in breast cancer.

scholarly journals CUL4A ubiquitin ligase: a promising drug target for cancer and other human diseases

Open Biology ◽  
2014 ◽  
Vol 4 (2) ◽  
pp. 130217 ◽  
Author(s):  
Puneet Sharma ◽  
Alo Nag
Keyword(s):  
Ubiquitin Ligase ◽  
Drug Target ◽  
Critical Role ◽  
Cellular Transformation ◽  
Biological Processes ◽  
Molecular Architecture ◽  
The Past ◽  
Cullin 4A ◽  
Broad Overview

The ability of cullin 4A (CUL4A), a scaffold protein, to recruit a repertoire of substrate adaptors allows it to assemble into distinct E3 ligase complexes to mediate turnover of key regulatory proteins. In the past decade, a considerable wealth of information has been generated regarding its biology, regulation, assembly, molecular architecture and novel functions. Importantly, unravelling of its association with multiple tumours and modulation by viral proteins establishes it as one of the key proteins that may play an important role in cellular transformation. Considering the role of its substrate in regulating the cell cycle and maintenance of genomic stability, understanding the detailed aspects of these processes will have significant consequences for the treatment of cancer and related diseases. This review is an effort to provide a broad overview of this multifaceted ubiquitin ligase and addresses its critical role in regulation of important biological processes. More importantly, its tremendous potential to be exploited for therapeutic purposes has been discussed.

scholarly journals Differential HspBP1 expression accounts for the greater vulnerability of neurons than astrocytes to misfolded proteins

2017 ◽  
Vol 114 (37) ◽  
pp. E7803-E7811 ◽  
Author(s):  
Ting Zhao ◽  
Yan Hong ◽  
Peng Yin ◽  
Shihua Li ◽  
Xiao-Jiang Li
Keyword(s):  
Neurodegenerative Diseases ◽  
Critical Role ◽  
Misfolded Proteins ◽  
Inhibitory Protein ◽  
Interacting Protein ◽  
C Terminus ◽  
Differential Vulnerability ◽  
Disease Protein ◽  
Knockin Mouse

Although it is well known that astrocytes are less vulnerable than neurons in neurodegenerative diseases, the mechanism behind this differential vulnerability is unclear. Here we report that neurons and astrocytes show markedly different activities in C terminus of Hsp70-interacting protein (CHIP), a cochaperone of Hsp70. In astrocytes, CHIP is more actively monoubiquitinated and binds to mutant huntingtin (mHtt), the Huntington’s disease protein, more avidly, facilitating its K48-linked polyubiquitination and degradation. Astrocytes also show the higher level and heat-shock induction of Hsp70 and faster CHIP-mediated degradation of various misfolded proteins than neurons. In contrast to astrocytes, neurons express abundant HspBP1, a CHIP inhibitory protein, resulting in the low activity of CHIP. Silencing HspBP1 expression via CRISPR-Cas9 in neurons ameliorated mHtt aggregation and neuropathology in HD knockin mouse brains. Our findings indicate a critical role of HspBP1 in differential CHIP/Hsp70 activities in neuronal and glial cells and the greater neuronal vulnerability to misfolded proteins in neurodegenerative diseases.

scholarly journals The role of Ubiquitination in Apoptosis and Necroptosis

2021 ◽  
Author(s):  
Jamie Z. Roberts ◽  
Nyree Crawford ◽  
Daniel B. Longley
Keyword(s):  
Cell Death ◽  
Death Receptors ◽  
Tnf Receptor ◽  
Extrinsic Pathway ◽  
Post Translational Modifications ◽  
Cell Death Pathways ◽  
Apoptotic Pathways ◽  
Extrinsic Apoptotic Pathways ◽  
Necrosis Factor

AbstractCell death pathways have evolved to maintain tissue homoeostasis and eliminate potentially harmful cells from within an organism, such as cells with damaged DNA that could lead to cancer. Apoptosis, known to eliminate cells in a predominantly non-inflammatory manner, is controlled by two main branches, the intrinsic and extrinsic apoptotic pathways. While the intrinsic pathway is regulated by the Bcl-2 family members, the extrinsic pathway is controlled by the Death receptors, members of the tumour necrosis factor (TNF) receptor superfamily. Death receptors can also activate a pro-inflammatory type of cell death, necroptosis, when Caspase-8 is inhibited. Apoptotic pathways are known to be tightly regulated by post-translational modifications, especially by ubiquitination. This review discusses research on ubiquitination-mediated regulation of apoptotic signalling. Additionally, the emerging importance of ubiquitination in regulating necroptosis is discussed.

scholarly journals Modulation of Neuroinflammation by the Gut Microbiota in Prion and Prion-Like Diseases

Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 887
Author(s):  
Josephine Trichka ◽  
Wen-Quan Zou
Keyword(s):  
Nervous System ◽  
Gut Microbiota ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disease ◽  
Peripheral Nervous System ◽  
Brain Parenchyma ◽  
Therapeutic Approaches ◽  
Microbial Metabolite ◽  
The Past

The process of neuroinflammation contributes to the pathogenic mechanism of many neurodegenerative diseases. The deleterious attributes of neuroinflammation involve aberrant and uncontrolled activation of glia, which can result in damage to proximal brain parenchyma. Failure to distinguish self from non-self, as well as leukocyte reaction to aggregation and accumulation of proteins in the CNS, are the primary mechanisms by which neuroinflammation is initiated. While processes local to the CNS may instigate neurodegenerative disease, the existence or dysregulation of systemic homeostasis can also serve to improve or worsen CNS pathologies, respectively. One fundamental component of systemic homeostasis is the gut microbiota, which communicates with the CNS via microbial metabolite production, the peripheral nervous system, and regulation of tryptophan metabolism. Over the past 10–15 years, research focused on the microbiota–gut–brain axis has culminated in the discovery that dysbiosis, or an imbalance between commensal and pathogenic gut bacteria, can promote CNS pathologies. Conversely, a properly regulated and well-balanced microbiome supports CNS homeostasis and reduces the incidence and extent of pathogenic neuroinflammation. This review will discuss the role of the gut microbiota in exacerbating or alleviating neuroinflammation in neurodegenerative diseases, and potential microbiota-based therapeutic approaches to reduce pathology in diseased states.

scholarly journals Therapeutic Effects of Melatonin on Ocular Diseases: Knowledge Map and Perspective

2021 ◽  
Vol 12 ◽  
Author(s):  
Haozhe Yu ◽  
Qicong Wang ◽  
Wenyu Wu ◽  
Weizhen Zeng ◽  
Yun Feng
Keyword(s):  
Clinical Evidence ◽  
Critical Role ◽  
Knowledge Map ◽  
Therapeutic Effects ◽  
Ocular Diseases ◽  
Ocular Tissues ◽  
The Past ◽  
Clinical Transformation ◽  
And Oxidative Stress

Melatonin plays a critical role in the pathophysiological process including circadian rhythm, apoptosis, and oxidative stress. It can be synthesized in ocular tissues, and its receptors are also found in the eye, triggering more investigations concentrated on the role of melatonin in the eye. In the past decades, the protective and therapeutic potentials of melatonin for ocular diseases have been widely revealed in animal models. Herein, we construct a knowledge map of melatonin in treating ocular diseases through bibliometric analysis and review its current understanding and clinical evidence. The overall field could be divided into twelve topics through keywords co-occurrence analysis, in which the glaucoma, myopia, and retinal diseases were of greatest research interests according to the keywords burst detection. The existing clinical trials of melatonin in ocular diseases mainly focused on the glaucoma, and more research should be promoted, especially for various diseases and drug administration. We also discuss its bioavailability and further research topics including developing melatonin sensors for personalized medication, acting as stem cell therapy assistant drug, and consuming food-derived melatonin for facilitating its clinical transformation.

scholarly journals News about the Role of the Transcription Factor REST in Neurons: From Physiology to Pathology

2019 ◽  
Vol 21 (1) ◽  
pp. 235 ◽  
Author(s):  
Jose M. Garcia-Manteiga ◽  
Rosalba D’Alessandro ◽  
Jacopo Meldolesi
Keyword(s):  
Transcription Factor ◽  
Neurodegenerative Diseases ◽  
The Other ◽  
Brain Diseases ◽  
Strong Decrease ◽  
Future Developments ◽  
The Past

RE-1 silencing transcription factor (REST) (known also as NRSF) is a well-known transcription repressor whose strong decrease induces the distinction of neurons with respect to the other cells. Such distinction depends on the marked increased/decreased expression of specific genes, accompanied by parallel changes of the corresponding proteins. Many properties of REST had been identified in the past. Here we report those identified during the last 5 years. Among physiological discoveries are hundreds of genes governed directly/indirectly by REST, the mechanisms of its neuron/fibroblast conversions, and the cooperations with numerous distinct factors induced at the epigenetic level and essential for REST specific functions. New effects induced in neurons during brain diseases depend on the localization of REST, in the nucleus, where functions and toxicity occur, and in the cytoplasm. The effects of REST, including cell aggression or protection, are variable in neurodegenerative diseases in view of the distinct mechanisms of their pathology. Moreover, cooperations are among the mechanisms that govern the severity of brain cancers, glioblastomas, and medulloblastomas. Interestingly, the role in cancers is relevant also for therapeutic perspectives affecting the REST cooperations. In conclusion, part of the new REST knowledge in physiology and pathology appears promising for future developments in research and brain diseases.

Precision medicine: Driving the evolution of biobanking quality

2020 ◽  
Vol 33 (3) ◽  
pp. 102-106 ◽  
Author(s):  
Rebecca O. Barnes ◽  
Peter H. Watson
Keyword(s):  
Data Quality ◽  
Precision Medicine ◽  
Healthcare System ◽  
Biological Samples ◽  
Critical Role ◽  
Quality Requirements ◽  
The Past ◽  
The Impact ◽  
Research Domain

The promise of precision medicine will only be realized if the healthcare system adapts to meet some key infrastructure needs. Among these needs are adequate biobanking practices, capable of producing the biological samples and data that precision medicine relies upon in both the research and clinical phases. Within the research domain, there have been significant improvements to biobanking processes over the past two decades, driven by increased understanding of the impact of pre-analytical variability and the critical role of biospecimen and data quality. In the era of precision medicine, biobanking to support clinical needs has similar quality requirements. The extensive knowledge and resources that have been developed by the research biobanking community are available for adoption by clinical biobanking. The challenge and opportunity now presented to the healthcare system is to adopt or adapt these resources, for example, external biobanking standards and verification programs.

Sign in / Sign up

Export Citation Format

Share Document