Research Topic

The Unfolded Protein Response and the integrated stress Response in Neuropathology and Brain Health

About this Research Topic

The most fundamental cellular decision, to adapt or die, hinges on the cell's ability to maintain homeostasis. The unfolded protein response (UPR) and the integrated stress response (ISR) are evolutionarily conserved signaling networks that maintain protein homeostasis—proteostasis. However, unrelenting proteotoxic stress triggers UPR/ISR-regulated programmed cell death pathways. Both outcomes, preserving healthy cells or eliminating terminally injured ones, are essential for maintaining tissues and organs. Numerous investigations over the past decade have underscored the profound implications of UPR/ISR overactivation and insufficiency in neuropathology, and highlight the fundamental roles of these homeostatic mechanisms in maintaining brain health. These investigations also underscore the potential for pharmacological manipulation of the UPR/ISR for therapeutic intervention in neuropathologies. This research topic focuses on the roles of the UPR/ISR in the nervous system and aims to showcase discoveries in neurobiology.

The extent to which the UPR/ISR regulate the brain's physiological processes remains an active area of investigation that will yield fruit for years to come. Many neuropathologies can be traced back to cell maintenance defects. For example, insufficient UPR/ISR signaling leads to cell loss in neuropathologies linked to protein aggregation. However, the roles of the UPR/ISR go beyond cell maintenance in neuropathology. Recent discoveries feature the ISR's role in cognition and memory consolidation, linking it to pathology or injury associated with cognitive decline.

In this Research Topic, we will welcome authors who wish to showcase their original research on the UPR/ISR roles and their fundamental cellular mechanisms in normal neural cell physiology, development, and disease states. The following topics are of particular interest:
• Regulation of neural cell plasticity by the UPR/ISR signaling dynamics in health and disease states
• Regulation of the UPR/ISR in neural stem cells and during neural cell differentiation
• Regulation of the UPR/ISR in different neural cell lineages and neural cell-states
• Repercussions of sex/gender differences in UPR/ISR signaling in neural cells
• Roles of cell non-autonomous UPR/ISR signaling in long-range control of stress responses
• Molecular mechanisms of crosstalk between the UPR/ISR and neural cell-specific signaling programs during differentiation, disease, and response to injury
• Opportunities for pharmacologic intervention targeting the UPR/ISR in neurodegeneration



Keywords: Unfolded protein response, Integrated stress response, Stress responses, Proteostasis, Neurological disorders, Neurodegeneration


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

The most fundamental cellular decision, to adapt or die, hinges on the cell's ability to maintain homeostasis. The unfolded protein response (UPR) and the integrated stress response (ISR) are evolutionarily conserved signaling networks that maintain protein homeostasis—proteostasis. However, unrelenting proteotoxic stress triggers UPR/ISR-regulated programmed cell death pathways. Both outcomes, preserving healthy cells or eliminating terminally injured ones, are essential for maintaining tissues and organs. Numerous investigations over the past decade have underscored the profound implications of UPR/ISR overactivation and insufficiency in neuropathology, and highlight the fundamental roles of these homeostatic mechanisms in maintaining brain health. These investigations also underscore the potential for pharmacological manipulation of the UPR/ISR for therapeutic intervention in neuropathologies. This research topic focuses on the roles of the UPR/ISR in the nervous system and aims to showcase discoveries in neurobiology.

The extent to which the UPR/ISR regulate the brain's physiological processes remains an active area of investigation that will yield fruit for years to come. Many neuropathologies can be traced back to cell maintenance defects. For example, insufficient UPR/ISR signaling leads to cell loss in neuropathologies linked to protein aggregation. However, the roles of the UPR/ISR go beyond cell maintenance in neuropathology. Recent discoveries feature the ISR's role in cognition and memory consolidation, linking it to pathology or injury associated with cognitive decline.

In this Research Topic, we will welcome authors who wish to showcase their original research on the UPR/ISR roles and their fundamental cellular mechanisms in normal neural cell physiology, development, and disease states. The following topics are of particular interest:
• Regulation of neural cell plasticity by the UPR/ISR signaling dynamics in health and disease states
• Regulation of the UPR/ISR in neural stem cells and during neural cell differentiation
• Regulation of the UPR/ISR in different neural cell lineages and neural cell-states
• Repercussions of sex/gender differences in UPR/ISR signaling in neural cells
• Roles of cell non-autonomous UPR/ISR signaling in long-range control of stress responses
• Molecular mechanisms of crosstalk between the UPR/ISR and neural cell-specific signaling programs during differentiation, disease, and response to injury
• Opportunities for pharmacologic intervention targeting the UPR/ISR in neurodegeneration



Keywords: Unfolded protein response, Integrated stress response, Stress responses, Proteostasis, Neurological disorders, Neurodegeneration


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Submission Deadlines

13 June 2021 Abstract
11 October 2021 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

13 June 2021 Abstract
11 October 2021 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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