Barbara Mordyl, Monika Marcinkowska

TSPO as a novel mitochondrial regulatory pathway in central nervous system disorders

2025-12-11

Research subject. TSPO (Translocator Protein) plays a pivotal role in mitochondrial physiology, being involved in cholesterol transport, maintenance of mitochondrial membrane integrity, ATP (Adenosine Triphosphate) synthesis, and regulation of apoptotic pathways. Moreover, TSPO has been characterized as a key modulator of immune responses and oxidative stress in central nervous system disorders, particularly in conditions of ischemic and neurodegenerative origin. Due to its functions and involvement in fundamental cellular processes, TSPO has emerged as a promising target for the development of novel therapeutic strategies.

Objective of the research. This review aims to summarize the current understanding of the structure, localization, and function of the TSPO protein, its interaction with the TMEM97 receptor (Transmembrane Protein 97), and the role of TSPO ligands in neuroprotection, PET imaging (Positron Emission Tomography), and mitochondria-targeted therapeutic strategies.

Materials and methods. The review was based on an analysis of scientific publications available in the PubMed, Scopus, and Web of Science databases. Original experimental and review articles concerning the structure and function of TSPO and its ligands, as well as their applications in the imaging and treatment of central nervous system disorders, were included in the study.

Results. The conducted study emphasizes the crucial role of the TSPO protein in the regulation of mitochondrial homeostasis, oxidative stress, and inflammatory responses, and further indicates its potential significance as a therapeutic target in ischemic and neurodegenerative disorders.

Discussion. The novelty of this work lies in demonstrating the potential interaction between TSPO and the TMEM97 receptor. The strengths of this study include its comprehensive perspective on the subject and the integration of molecular, pharmacological, and neurobiological findings. The main limitation is the finite number of translational and clinical studies that could confirm the effectiveness of TSPO-TMEM97 complex modulation in humans. Compared with previous analyses, the present review places greater emphasis on the importance of interorganelle interactions and their influence on neuroprotective processes. Variations in results among studies may arise from differences in experimental models, the ligands applied, and the methods used to assess TSPO expression. The significance of these findings is considerable for researchers, as they suggest the possibility of developing new therapeutic strategies based on the modulation of TSPO activity. Moreover, these conclusions may serve as a foundation for future research on targeted therapies in neurodegenerative diseases. Nevertheless, the precise mechanism underlying the interaction between TSPO and TMEM97, as well as the long-term effects of modulating this complex on cellular functions, remains to be fully elucidated.

Conclusions. The conducted study highlights the pivotal role of the TSPO protein in maintaining mitochondrial homeostasis and regulating oxidative stress and inflammatory responses, particularly in the context of central nervous system disorders. It has been demonstrated that the interaction between TSPO and the TMEM97 receptor may form a novel signaling axis between mitochondria and the endoplasmic reticulum, influencing the balance between neuroprotective processes and apoptosis. The discovery of this relationship opens new perspectives for the development of targeted therapies, which, through modulation of the TSPO-TMEM97 complex, could represent an effective strategy for the treatment of ischemic stroke and other neurodegenerative disorders.

Keywords: TSPO, TMEM97, mitochondria, neuroprotection, oxidative stress, TSPO ligands.

© Farm Pol, 2025, 81(5): 255–265