REVIEW: Unique Properties of Synaptosomes and Prospects for Their Use for the Treatment of Alzheimer’s Disease

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Alla S. Dashkova^1#, Vladimir I. Kovalev^1,a*#, Alina V. Chaplygina¹, Daria Yu. Zhdanova¹, Natalia V. Bobkova¹

¹Institute of Cell Biophysics, Russian Academy of Sciences, 142290 Pushchino, Moscow Region, Russia

^* To whom correspondence should be addressed.

^# These authors contributed equally to the work.

Received: October 25, 2023; Revised: March 21, 2024; Accepted: March 23, 2024

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Alzheimer’s disease (AD) is a severe neurodegenerative condition affecting millions worldwide. Prevalence of AD correlates with increased life expectancy and aging population in the developed countries. Considering that AD is a multifactorial disease involving various pathological processes such as synaptic dysfunction, neuroinflammation, oxidative stress, and improper protein folding, a comprehensive approach targeting multiple pathways may prove effective in slowing the disease progression. Cellular therapy and its further development in the form of cell vesicle and particularly mitochondrial transplantation represent promising approaches for treating neurodegeneration. The use of synaptosomes, due to uniqueness of their contents, could mark a new stage in the development of comprehensive therapies for neurodegenerative diseases, particularly AD. Synaptosomes contain unique memory mitochondria, which differ not only in size but also in functionality compared to the mitochondria in the neuronal soma. These synaptosomal mitochondria actively participate in cellular communication and signal transmission within synapses. Synaptosomes also contain other elements such as their own protein synthesis machinery, synaptic vesicles with neurotransmitters, synaptic adhesion molecules, and microRNAs – all crucial for synaptic transmission and, consequently, cognitive processes. Complex molecular ensemble ensures maintenance of the synaptic autonomy of mitochondria. Additionally, synaptosomes, with their affinity for neurons, can serve as an optimal platform for targeted drug delivery to nerve cells. This review discusses unique composition of synaptosomes, their capabilities and advantages, as well as limitations of their suggested use as therapeutic agents for treating neurodegenerative pathologies, particularly AD.

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KEY WORDS: Alzheimer’s disease, mitochondria, neurodegenerative diseases, memory, synaptosomes

DOI: 10.1134/S0006297924060051

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