3‐hydroxybutyrate in the brain: Biosynthesis, function, and disease therapy

Author:

Wang Bing‐Long1,Wu Jian‐Fei1,Xiao Da2,Wu Bo3,Wei Dai‐Xu14ORCID

Affiliation:

1. Zigong Affiliated Hospital of Southwest Medical University Zigong Psychiatric Research Center Zigong Institute of Brain Science Zigong Sichuan Province China

2. Department of Chemical System Engineering The University of Tokyo Tokyo Japan

3. Department of Biochemistry and Structural Biology University of Texas Health San Antonio San Antonio Texas USA

4. Key Laboratory of Resource Biology and Biotechnology in Western China Department of Life Sciences and Medicine Ministry of Education School of Medicine Northwest University Xi'an Shaanxi Province China

Abstract

Abstract3‐hydroxybutyrate (3HB), or BHB, is an anionic small molecule acid metabolite with a hydroxyl group. 3HB is the major ketone body that is distributed in the human brain and its primary energy source when glucose is absent. A better understanding of 3HB and how to adapt neuronal response mechanisms is expected to facilitate the development of new interventions to promote cognitive brain function and prevent neurodegenerative diseases. It provides important concepts for the clinical application of 3HB therapy. This review summarizes the distribution of 3HB in the brain, its properties, and its mechanism in brain and nerve regulation. We focus on 3HB biosynthesis in natural human cells and engineered bacteria via synthetic biology platforms and 3HB treatment in various brain and nerve diseases, including epilepsy, multiple sclerosis, stroke, Parkinson's disease, Alzheimer's disease, Huntington's disease, depressive disorder, and schizophrenia. Ultimately, this review explores the future development trend of 3HB as a potential small‐molecule drug for brain and nerve diseases.

Funder

National Natural Science Foundation of China

Publisher

Wiley

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