Over the last two decades, many experimental and clinical studies have provided solid evidence that alpha-synuclein (α-syn), a small, natively unfolded protein, is closely related to Parkinson’s disease (PD) pathology. In order to provide an overview on the different roles of this protein, here we propose a synopsis of seminal and recent studies that explored the many aspects of α-syn. Ranging from the physiological functions to its neurodegenerative potential, the relationship with the possible pathogenesis of PD will be discussed. Close attention will be paid on early cellular and molecular alterations associated to the presence of α-syn aggregates.

/pdf/alpha-synuclein-from-early-synaptic-dysfunction-to-5bli4k8ted.pdf

Alpha-Synuclein: From Early Synaptic Dysfunction to Neurodegeneration.

How Financial Constraints Influence Consumer Behavior: An Integrative Framework

Neuroinflammation is a process involved in the pathogenesis of different disorders, both autoimmune, such as neuropsychiatric systemic lupus erythematosus, and degenerative, such as Alzheimer’s and Parkinson’s disease. In the central nervous system, the local milieu is tightly regulated by different mediators, among which are chemoattractant cytokines, also known as chemokines. These small molecules are able to modulate trafficking of immune cells in the course of nervous system development or in response to tissue damage, and different patterns of chemokine molecule and receptor expression have been described in several neuroinflammatory disorders. In recent years, a number of studies have highlighted a pivotal role of sphingolipids in regulating neuroinflammation. Sphingolipids have different functions, among which are the control of leukocyte egress from lymphonodes into inflamed tissues, the expression of various mediators of inflammation and a direct effect on the cells of the central nervous system as regulators of neuroinflammation. In the future, a better knowledge of these two groups of mediators could provide insight into the pathogenesis of neuroinflammatory disorders and could help develop novel diagnostic tools and therapeutic strategies.

Modulation of Neuroinflammation in the Central Nervous System: Role of Chemokines and Sphingolipids

Parkinson's disease (PD) is an aging-associated neurodegenerative disease with a characteristic feature of α-synuclein accumulation. Point mutations (A53T, A30P) that increase the aggregation propensity of α-synuclein result in familial early onset PD. The abnormal metabolism of α-synuclein results in aberrant level changes of α-synuclein in PD. In pathological conditions, α-synuclein is degraded mainly by the autophagy-lysosome pathway. Triptolide (T10) is a monomeric compound isolated from a traditional Chinese herb. Our group demonstrated for the first time that T10 possesses potent neuroprotective properties both in vitro and in vivo PD models. In the present study, we reported T10 as a potent autophagy inducer in neuronal cells, which helped to promote the clearance of various forms of α-synuclein in neuronal cells. We transfected neuronal cells with A53T mutant (A53T) or wild-type (WT) α-synuclein plasmids and found T10 attenuated the cytotoxicity induced by pathogenic A53T α-synuclein overexpression. We observed that T10 significantly reduced both A53T and WT α-synuclein level in neuronal cell line, as well as in primary cultured cortical neurons. Excluding the changes of syntheses, secretion, and aggregation of α-synuclein, we further added autophagy inhibitor or proteasome inhibitor with T10, and we noticed that T10 promoted the clearance of α-synuclein mainly by the autophagic pathway. Lastly, we observed increased autophagy marker LC3-II expression and autophagosomes by GFP-LC3-II accumulation and ultrastructural characterization. However, the lysosome activity and cell viability were not modulated by T10. Our study revealed that T10 could induce autophagy and promote the clearance of both WT and A53T α-synuclein in neurons. These results provide evidence of T10 as a promising mean to treat PD and other neurodegenerative diseases by reducing pathogenic proteins in neurons.

Triptolide Promotes the Clearance of α-Synuclein by Enhancing Autophagy in Neuronal Cells

Social media users’ online subjective well-being and fatigue: A network heterogeneity perspective

This article studies the interplay between Siddha medicine and Santhigiri, a Hindu guru organization in South India. Based on insights gained through ethnographic research in Kerala and Tamil Nadu, it analyzes how Santhigiri fashions itself as an indispensable actor in the restoration of Siddha medicine and valorizes its current Siddha medical activities. The article examines the dynamics that facilitate Santhigiri’s patronage of Siddha medicine and contribute to its continuing participation in the Siddha medical system. This social formation is conceptualized through the Bourdieusian framework of capital, arguing that Santhigiri’s appropriation of Siddha medicine bestows symbolic capital upon the organization, enabling it to secure and maintain a favorable position in the field of Hindu guru organizations. Furthermore, the article shows how, by adopting Siddha medicine, a religious organization such as Santhigiri with the necessary structural and financial means and a reputation for transcending economic interests extends the distribution of Siddha medicine beyond the Tamil community. Thus, the article emphasizes the reciprocal relationship between a religious organization and a medical system, arguing for the explanatory potential of conceiving of medicine as effective capital for religious organizations and, vice versa, of religious organizations as actors shaping the realm of medicine in India.

A Reciprocal Relationship: Siddha Medicine in the Context of a Hindu Guru Organization

Zusammenfassung: Vor dem Hintergrund von Deinstitutionalisierungsprozessen Neuer religioser Gemeinschaften tritt die Gemeinschaft Auroville als bemerkenswertes Kontrastbeispiel auf, besteht sie namlich seit ihrer Grundung 1968 in der gemeinschaftlichen Form. Von dieser Beobachtung ausgehend, steht die Frage nach den Bedingungen zur Konstitution und Aufrechterhaltung der Gemeinschaft im Zentrum dieses Aufsatzes. Mit Blick auf das Erklarungsmuster aus der Durkheim- Parsons-Tradition zur Konstitution religioser Gemeinschaften, welches uber das Konzept der Wertintegration verlauft, wird die Frage diskutiert, welche Rolle dem religiosen Symbolsystem Aurovilles in der Aufrechterhaltung der Gemeinschaft zukommt. Anhand des Freiheits- respektive Individualisierungsnarratives, das sich bei der zweiten Generation als identifikatorisches Moment durchgesetzt hat, lasst sich zeigen, dass nicht die gemeinschaftlichen Werte, sondern der lebenspraktische Bedingungsrahmen die Individuen in die Gemeinschaft einbindet.
With the deinstitutionalization of new religious movements, the religious community Auroville provides an important counter-example: Auroville has remained its communal type of social relationship since its inception in 1968. Through qualitative interviews with second generation community members this article thus examines the conditions that maintain Auroville as a community. The article particularly explores the significance of the religious symbol system of Auroville for the constitution of the community and thereby also evaluates ideas regarding the concept of value-integration from the Durkheim-Parsons-tradition. By analyzing the notion of freedom and individualization this paper argues that the ideals of the community lack importance in strengthening the ties between the second generation and the broader community. Rather, the second generation has created a narrative about the distinct features of living in Auroville that encourages them to remain in the community.

/pdf/gemeinschaft-in-der-zweiten-generation-53ekophnl7.pdf

Nina Rageth

Papers

A Reciprocal Relationship: Siddha Medicine in the Context of a Hindu Guru Organization

Gemeinschaft in der zweiten Generation