Role of SIRT1 in sepsis-induced encephalopathy: Molecular targets for future therapies

Sepsis induces neuroinflammation, BBB disruption, cerebral hypoxia, neuronal mitochondrial dysfunction, and cell death causing sepsis-associated encephalopathy (SAE). These pathological consequences lead to short- and long-term neurobehavioural deficits. Till now there is no specific treatment that...

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Bibliographic Details
Published in:The European journal of neuroscience 2023-11, Vol.58 (10), p.4211-4235
Main Authors: Shehata, Alaa H, Anter, Aliaa F, Ahmed, Al-Shaimaa F
Format: Article
Language:English
Subjects:
Brain injury
Cell death
Deacetylation
Encephalopathy
Forkhead protein
Humans
Hypoxia
Inflammation
Neuroinflammatory Diseases
Neuroprotection
Neuroprotective Agents - pharmacology
Neuroprotective Agents - therapeutic use
Sepsis
Sepsis - complications
Sepsis - metabolism
Sepsis - pathology
Sepsis-Associated Encephalopathy
SIRT1 protein
Sirtuin 1 - metabolism
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Summary:Sepsis induces neuroinflammation, BBB disruption, cerebral hypoxia, neuronal mitochondrial dysfunction, and cell death causing sepsis-associated encephalopathy (SAE). These pathological consequences lead to short- and long-term neurobehavioural deficits. Till now there is no specific treatment that directly improves SAE and its associated behavioural impairments. In this review, we discuss the underlying mechanisms of sepsis-induced brain injury with a focus on the latest progress regarding neuroprotective effects of SIRT1 (silent mating type information regulation-2 homologue-1). SIRT1 is an NAD -dependent class III protein deacetylase. It is able to modulate multiple downstream signals (including NF-κB, HMGB, AMPK, PGC1α and FoxO), which are involved in the development of SAE by its deacetylation activity. There are multiple recent studies showing the neuroprotective effects of SIRT1 in neuroinflammation related diseases. The proposed neuroprotective action of SIRT1 is meant to bring a promising therapeutic strategy for managing SAE and ameliorating its related behavioural deficits.
ISSN:0953-816X
1460-9568
DOI:10.1111/ejn.16167