E-ISSN 2475-0581
 

Review Article 


A Link Between PKR, Inflammasome and Synaptic Plasticity: Is it an Emerging Therapeutic Option for Cognitive Dysfunction?

Demet Sinem Guden, Feyza Aricioglu.

Abstract
A cognitive decline biomarker candidate, RNA-dependent protein kinase R (PKR), is proposed to play a crucial role on inflammation, and psychiatric disorders through prolonged metabolic stress, cellular and molecular imbalance by regulating central cellular processes including mRNA translation, transcriptional control, apoptosis, and cell proliferation. PKR is an interferon-induced serine/threonine protein kinase and a well-known master regulator of protein synthesis via phosphorylating the translation initiation factor α (eIF2α). Inflammasome assembly consists of large multiprotein complexes that are activated by the pathogen or damage-associated signals resulting in the formation of pro-inflammatory cytokines such as interleukin-1β (IL-1β), IL-18, and high-mobility group box 1 (HMGB1) protein. Release of proinflammatory cytokines and chemokines triggered by the hosts innate immune response against harmful pathogens coordinated by inflammasomes. PKR is involved in several cellular pathways including innate immunity and defense against viruses like inflammasomes. The upstream molecular mechanisms underlying the regulation of inflammasome activation poorly identified. Here, we focused on the role of PKR on the regulation of inflammasome assembly formation by summarizing current investigations that are linked to inflammation/neuroinflammation-driven synaptic plasticity. Virus, inflammatory, and toxic cellular signals activate this protein kinase and is responsible for translation initiation blockade via its downstream target. PKR activation also contributes to inflammation and immune dysfunction through the regulation of inflammatory cell signaling pathways. Cytokines regulated by inflammasomes are critical mediators of psychiatric diseases and neurodegenerative disorders. Previous works have suggested that systemic inflammation could contribute to neuroinflammation and related neurodegeneration via activation of inflammasome assembly. Previous researches found that PKR physically interacted with different inflammasomes. Recent investigations highlighted a key role for PKR in the regulation of inflammasome-mediated diseases and cognitive function. PKR might be a valid target to modulate neuroinflammation and neurodegeneration by modulating inflammasomes. Hence, it is conceivable to hypothesize that PKR could be a pharmacologically alluring objective for treating neuroinflammatory diseases by modulating inflammasome activation in parallel with learning and memory deficits. In the future, the assessment of this kinase levels in the blood of patients would enable us to find novel biomarkers to struggle neuroinflammatory process in neurodegenerative and psychiatric diseases.

Key words: PKR, inflammation, inflammasome, synaptic plasticity


 
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How to Cite this Article
Pubmed Style

Guden DS, Aricioglu F. A Link Between PKR, Inflammasome and Synaptic Plasticity: Is it an Emerging Therapeutic Option for Cognitive Dysfunction?. Psychiatry and Clinical Psychopharmacology - PCP. 2020; 30(3): 313-320. doi:10.5455/PCP.20200801015342


Web Style

Guden DS, Aricioglu F. A Link Between PKR, Inflammasome and Synaptic Plasticity: Is it an Emerging Therapeutic Option for Cognitive Dysfunction?. http://www.psychiatryandclinicalpsychopharmacology.org/?mno=117134 [Access: October 02, 2020]. doi:10.5455/PCP.20200801015342


AMA (American Medical Association) Style

Guden DS, Aricioglu F. A Link Between PKR, Inflammasome and Synaptic Plasticity: Is it an Emerging Therapeutic Option for Cognitive Dysfunction?. Psychiatry and Clinical Psychopharmacology - PCP. 2020; 30(3): 313-320. doi:10.5455/PCP.20200801015342



Vancouver/ICMJE Style

Guden DS, Aricioglu F. A Link Between PKR, Inflammasome and Synaptic Plasticity: Is it an Emerging Therapeutic Option for Cognitive Dysfunction?. Psychiatry and Clinical Psychopharmacology - PCP. (2020), [cited October 02, 2020]; 30(3): 313-320. doi:10.5455/PCP.20200801015342



Harvard Style

Guden, D. S. & Aricioglu, . F. (2020) A Link Between PKR, Inflammasome and Synaptic Plasticity: Is it an Emerging Therapeutic Option for Cognitive Dysfunction?. Psychiatry and Clinical Psychopharmacology - PCP, 30 (3), 313-320. doi:10.5455/PCP.20200801015342



Turabian Style

Guden, Demet Sinem, and Feyza Aricioglu. 2020. A Link Between PKR, Inflammasome and Synaptic Plasticity: Is it an Emerging Therapeutic Option for Cognitive Dysfunction?. Psychiatry and Clinical Psychopharmacology, 30 (3), 313-320. doi:10.5455/PCP.20200801015342



Chicago Style

Guden, Demet Sinem, and Feyza Aricioglu. "A Link Between PKR, Inflammasome and Synaptic Plasticity: Is it an Emerging Therapeutic Option for Cognitive Dysfunction?." Psychiatry and Clinical Psychopharmacology 30 (2020), 313-320. doi:10.5455/PCP.20200801015342



MLA (The Modern Language Association) Style

Guden, Demet Sinem, and Feyza Aricioglu. "A Link Between PKR, Inflammasome and Synaptic Plasticity: Is it an Emerging Therapeutic Option for Cognitive Dysfunction?." Psychiatry and Clinical Psychopharmacology 30.3 (2020), 313-320. Print. doi:10.5455/PCP.20200801015342



APA (American Psychological Association) Style

Guden, D. S. & Aricioglu, . F. (2020) A Link Between PKR, Inflammasome and Synaptic Plasticity: Is it an Emerging Therapeutic Option for Cognitive Dysfunction?. Psychiatry and Clinical Psychopharmacology, 30 (3), 313-320. doi:10.5455/PCP.20200801015342