Re:케톤체(베타-하이드록시뷰티레이트)로 파킨슨병의 복합병리를 개선해는 기전에 관한 2019년 논문

[문형철]

beyond reason

케톤체(베타-하이드록시뷰티레이트)로 파킨슨병의 복합병리를 개선해는 기전에 관한 2019년 논문

norwitz2019.pdf

The Mechanisms by Which the Ketone Body D-b-Hydroxybutyrate May Improve the Multiple Cellular Pathologies of Parkinson’s Disease

 Parkinson’s disease, a progressive neurodegenerative disorder characterized by motor

and non-motor symptoms, is strongly associated with the death of dopaminergic

neurons in the brain’s substantia nigra. Although dopamine replacement therapy

temporarily helps patients manage their motor symptoms, this current standard of care

fails to address the underlying network of pathologies that contribute to the persistent

death of dopaminergic neurons. Thus, new treatment approaches are needed that

address the underlying pathologies and, thereby, slow or halt the progression of the

actual disease. D-b -hydroxybutyrate – a ketone body produced by the liver to support

brain function during periods of starvation – may provide an option. Lifestyle interventions

that induce endogenous D-b -hydroxybutyrate production, such as caloric restriction and

ketogenic diets, are known to increase healthspan and lifespan in animal models and are

used to treat neurological disorders. The efficacy of these ketosis-inducing interventions,

along with the recent development of commercially available D-b -hydroxybutyrate-based

nutritional supplements, should inspire interest in the possibility that D-b -hydroxybutyrate

itself exerts neuroprotective effects. This review provides a molecular model to

justify the further exploration of such a possibility. Herein, we explore the cellular

mechanisms by which the ketone body, D-b -hydroxybutyrate, acting both as ametabolite

and as a signaling molecule, could help to prevent the development, or slow the

progression of, Parkinson’s disease. Specifically, the metabolism of D-b -hydroxybutyrate

may help neurons replenish their depleted ATP stores and protect neurons against

oxidative damage. As a G-protein-coupled receptor ligand and histone deacetylase

inhibitor, D-b -hydroxybutyrate may further protect neurons against energy deficit

and oxidative stress, while also decreasing damaging neuroinflammation and death

by apoptosis. Restricted to the available evidence, our model relies largely upon  the interpretation of data from the separate literatures on the cellular effects of

D-b -hydroxybutyrate and on the pathogenesis of Parkinson’s disease. Future studies

are needed to reveal whether D-b -hydroxybutyrate actually has the potential to serve as

an adjunctive nutritional therapy for Parkinson’s disease.

Keywords: apoptosis, dopamine, D-b-hydroxybutyrate, energy metabolism, inflammation, oxidative stress, Parkinson’s disease