Exosome-Mediated Mitochondrial Regulation: A Promising Therapeutic Tool for Alzheimer’s Disease and Parkinson’s Disease

Young Hyun Jung,1,* Hyo Youn Jo,2,3,* Dae Hyun Kim,2,3 Yeon Ju Oh,2,3 Minsoo Kim,1 Seunghyun Na,1 Ho-Yeon Song,4 Hyun Jik Lee2,3 1Department of Physiology, College of Medicine, Soonchunhyang University, Cheonan, 31151, Republic of Korea; 2Laboratory of Veterinary Physiology, College of Veterinary Medicine and Veterinary Medicine Center, Chungbuk National University, Cheongju 28644, Republic of Korea; 3Institute for Stem Cell & Regenerative Medicine (ISCRM), Chungbuk National University, Cheongju, 28644, Republic of Korea; 4Department of Microbiology and Immunology, School of Medicine, Soonchunhyang University, Cheonan-si, 31151, Republic of Korea*These authors contributed equally to this workCorrespondence: Hyun Jik Lee, College of Veterinary Medicine, Chungbuk National University, Cheongju, 28644, Republic of Korea, Tel +82-43-261-2597, Email [email protected]: Alzheimer’s disease (AD) and Parkinson’s disease (PD) are representative neurodegenerative diseases with abnormal energy metabolism and altered distribution and deformation of mitochondria within neurons, particularly in brain regions such as the hippocampus and substantia nigra. Neurons have high energy demands; thus, maintaining a healthy mitochondrial population is important for their biological function. Recently, exosomes have been reported to have mitochondrial regulatory potential and antineurodegenerative properties. This review presents the mitochondrial abnormalities in brain cells associated with AD and PD and the potential of exosomes to treat these diseases. Specifically, it recapitulates research on the molecular mechanisms whereby exosomes regulate mitochondrial biogenesis, fusion/fission dynamics, mitochondrial transport, and mitophagy. Furthermore, this review discusses exosome-triggered signaling pathways that regulate nuclear factor (erythroid-derived 2)-like 2-dependent mitochondrial antioxidation and hypoxia inducible factor 1α-dependent metabolic reprogramming. In summary, this review aims to provide a profound understanding of the regulatory effect of exosomes on mitochondrial function in neurons and to propose exosome-mediated mitochondrial regulation as a promising strategy for AD and PD. Keywords: neurodegenerative disease, Alzheimer’s disease, Parkinson’s disease, exosome, mitochondria