Interplay between Notch and p53 promotes neuronal cell death in ischemic stroke

Balaganapathy, Priyanka,Baik, Sang-Ha,Mallilankaraman, Karthik,Sobey, Christopher G,Jo, Dong-Gyu,Arumugam, Thiruma V SAGE Publications 2018 Journal of cerebral blood flow and metabolism Vol.38 No.10

<P> Stroke is the world's second leading cause of mortality, with a high incidence of morbidity. Numerous neuronal membrane receptors are activated by endogenous ligands and may contribute to infarct development. Notch is a well-characterized membrane receptor involved in cell differentiation and proliferation, and now shown to play a pivotal role in cell death during ischemic stroke. Blockade of Notch signaling by inhibition of γ-secretase, an enzyme that generates the active form of Notch, is neuroprotective following stroke. We have also identified that Pin1, a peptidyl-prolyl isomerase that regulates p53 transactivation under stress, promotes the pathogenesis of ischemic stroke via Notch signaling. Moreover, Notch can also mediate cell death through a p53-dependent pathway, resulting in apoptosis of neural progenitor cells. The current study has investigated the interplay between Notch and p53 under ischemic stroke conditions. Using pharmacological inhibitors, we have demonstrated that a Notch intracellular domain (NICD)/p53 interaction is involved in transcriptional regulation of genes downstream of p53 and NICD to modify stroke severity. Furthermore, the NICD/p53 interaction confers stability to p53 by rescuing it from ubiquitination. Together, these results indicate that Notch contributes to the pathogenesis of ischemic stroke by promoting p53 stability and signaling. </P>

Notch signaling and neuronal death in stroke

Arumugam, Thiruma V.,Baik, Sang-Ha,Balaganapathy, Priyanka,Sobey, Christopher G.,Mattson, Mark P.,Jo, Dong-Gyu Elsevier 2018 Progress in neurobiology Vol.165 No.-

<P><B>Abstract</B></P> <P>Ischemic stroke is a leading cause of morbidity and death, with the outcome largely determined by the amount of hypoxia-related neuronal death in the affected brain regions. Cerebral ischemia and hypoxia activate the Notch1 signaling pathway and four prominent interacting pathways (NF-κB, p53, HIF-1α and Pin1) that converge on a conserved DNA-associated nuclear multi-protein complex, which controls the expression of genes that can determine the fate of neurons. When neurons experience a moderate level of ischemic insult, the nuclear multi-protein complex up-regulates adaptive stress response genes encoding proteins that promote neuronal survival, but when ischemia is more severe the nuclear multi-protein complex induces genes encoding proteins that trigger and execute a neuronal death program. We propose that the nuclear multi-protein transcriptional complex is a molecular mediator of neuronal hormesis and a target for therapeutic intervention in stroke.</P> <P><B>Highlights</B></P> <P> <UL> <LI> We review the roles of Notch in the neuropathology of ischemic stroke. </LI> <LI> We discuss the mechanisms for how Notch interacts with other gene transcription regulators such as HIF-1α, NF-κB, p53 and Pin1 following a stroke. </LI> <LI> We introduce a novel concept of a multi-protein complex which controls the expression of genes that determine the fate of neurons in stroke. </LI> <LI> We discuss if and how the multi-protein complex may regulate neuronal plasticity and resilience during the remodeling phase following stroke. </LI> <LI> We conclude with a perspective on how this research may lead to novel approaches for clinical intervention in ischemic stroke. </LI> </UL> </P>

Youth participation in Democratic Politics: Impediments and prospects

Balaganapathi Devarakonda,Nidhi Jarwal 한국외국어대학교 인도연구소 2022 남아시아연구 Vol.27 No.4

Democracy is the most preferred form of government in the contemporary world as it facilitates citizens' active political participation, which is considered its strength. The fundamental definition of democracy, "the rule of people," highlights that every citizen, irrespective of social, gender, or cultural differences, is both the ruler and the ruled simultaneously. One of the significant segments of the population of every democratic state is its youth. As youth is considered the country’s future, possessing a substantial segment of youth is ideal for a vibrant, dynamic, and developed country. Today youth is doing wonders in most fields like sports, entrepreneurship, information technology, administration, and so on, but remain underrepresented in politics in many world countries. Therefore, this paper analyses the place of youth at different forms of political participation in democracy as they represent the future of national and global politics. The paper aims to study the value of youth in the politics of democratic states and to estimate the hurdles in their political participation, such as individual obstacles, social and cultural concerns, problems of political institutions, and issues of civic education. To make a long-term difference, young people should have adequate representation in political institutions, processes, and decision making. The methodologies that this paper adopts are analytical and exploratory in assessing the place of youth in political participation and explicating the causes for their underrepresentation in politics. It provides a citizen's perspective to understanding politics and political participation in democracy. It assesses various forms of political participation and analyses youth participation in them. The basic argument of this paper is youth is indifferent and apathetic to politics. They are not involved in formal political participation, so they are absent in formal politics, political institutions, and decision-making. The need to make youth aware of their rights and duties and improve their representation in politics in a meaningful way is stressed in the discussion. The research questions for this paper are: What are youth's place and role in political participation? Are young people indifferent to politics? Why do young people not get opportunities to be involved in formal politics? What are the reasons for the underrepresentation of youth in politics? This study responds to these questions and provides some suggestions to improve the political participation of youth in democracy. This paper is structured in three sections. The first discusses ‘the meaning, role, and forms of political participation,’ and the second, with ‘youth and political participation’ to analyse the place of youth in politics and discuss reasons for improving the same. The paper’s third section deals with the obstacles youth face in political participation, followed by a conclusion that provides suggestions for strengthening youth participation in democracy.

Hinduism in Thailand

Balaganapathi Devarakonda 한국외국어대학교 인도연구소 2018 남아시아연구 Vol.24 No.2

My endeavor in this paper is to explore the presences and absences of Hinduism in contemporary Thailand. After addressing the methodological and conceptual difficulties in understanding ‘Hinduism’, I provide a brief glance of the history to give a bird’s eye view of the place of Hinduism in Thailand. Subsequently, I discuss the dynamics of the religious scape of Thailand as it is available in the form of heuristic models presented as ‘syncretic, compartmentlist and hybrid’ in the recent academic debates which have enriched the discourse. We understand that the discourse is thereby indirectly limiting any possibility of making a generalization about the presence or absence of any particular religion. Finally, I provide the dynamics of Hinduism in contemporary Thailand while interrogating the proclamation of Justin McDaniel that “there is no Hinduism in Thailand” by pointing out the conceptual limitations of his approach. The study limits itself to the contemporary academic landscape of Thai religions.