β-Hydroxybutyrate Regulates Activated Microglia to Alleviate Neurodegenerative Processes in Neurological Diseases: A Scoping Review

Abstract

This scoping review aimed to summarise the effects of the ketone body β-hydroxybutyrate. The review details the revealed pathways and functional properties following its intervention in the context of neurodegenerative diseases. In this study, 5 research publications that met the inclusion and exclusion criteria were shortlisted. Following the intervention, we discovered a tendency of reduced inflammatory status in microglia, as evidenced by lower levels of pro-inflammatory mediators produced, reduced microgliosis in afflicted tissues, and enhanced cognitive functions in neurodegenerative models. We found that there is a significant overlap in the mechanism of action of b-hydroxybutyrate (BHB) via activation of the G-protein-Coupled Receptor 109A (GPR109a) receptor and deactivation of the inflammasome complex. Furthermore, although comparing outcomes can be challenging due to the heterogeneity in the study model, the results we have assembled here were consistent, giving us confidence in the intervention’s efficacy. We also discussed new studies where BHB is involved in various roles in regulating inflammation in microglia, allowing for fresh therapeutic targets against neurodegeneration. This brief review provides evidence to support the huge potential of BHB in the treatment of neurodegenerative illnesses.

Ketone Bodies Rescue Mitochondrial Dysfunction Via Epigenetic Remodeling

“…Nevertheless, therapeutic applications of BHB have been mainly considered in neurologic disorders and cancer. 14 , 20 , 21 Several investigators have propounded that the shift toward ketone bodies’ metabolism could be adaptive and beneficial in cardiac ischemia/reperfusion injury. 7 , 22 , 23 Yet the studies currently available have focused on BHB as a mere carrier of energy, whilst its signaling pathways have been definitely underinvestigated.…”

Modulation of beta-hydroxybutyrate in traumatic brain injury

“…Ketone bodies are efficiently utilized by the brain, leading to elevated cytosolic succinate levels that inhibit prolyl hydroxylases and stabilize hypoxia-inducible factor 1 (HIF1). This stabilization of HIF1, facilitated by ketosis, contributes to the regulation of the interleukin-10 ( IL-10 ) gene, thereby controlling the production of inflammatory cytokines and ultimately safeguarding neurons [25 ▪ ,26,27].…”

Molecular Mechanisms of Neuroprotection by Ketone Bodies and Ketogenic Diet in Cerebral Ischemia and Neurodegenerative Diseases

“…Neuroinflammation constitutes a pivotal pathological feature in ischemic stroke and neurodegenerative diseases. The management of neuroinflammation emerges as a crucial strategy to prevent and treat nerve damage in neurological diseases [ 86 , 159 , 160 , 161 ]. KBs function as signaling molecules, orchestrating various cellular responses, encompassing inflammatory and immune functions [ 2 , 10 ].…”

“…BHB alleviates the neurodegenerative processes by regulating activated microglia and astrocytes [ 159 , 161 , 179 , 180 ]. BHB exhibits anti-inflammatory neuroprotection by inducing anti-inflammatory M2-type macrophage polarization through HDAC inhibition-triggered Akt/RhoGTPase axis [ 181 ].…”