Structure and Function of TSPO (18 kDa Translocator Protein) and Its Role in Pathological Processes

Abstract

TSPO, which is pharmacologically and structurally different from central benzodiazepine receptors, was first discovered as a binding site for diazepam in the kidney and was defined as a "peripheral benzodiazepine receptor" due to its location outside the brain. It was later renamed "18 kDa Translocator Protein (18 kDa TSPO)" because it was found to be highly abundant in glial cells, endothelial cells and some neuron populations in the central nervous system as well as peripheral tissues. TSPO, which is located on the outer membrane of mitochondria, plays a role in many important processes such as steroid synthesis, proliferation, inflammation and apoptosis by transporting cholesterol into mitochondria. Various TSPO ligands, especially Ro5-4864 and PK11195, are used to investigate the effects of TSPO in different pathologies. TSPO and its ligands have become important pharmacological targets in the diagnosis and treatment of neurodegenerative diseases such as Alzheimer's disease (AD), frontotemporal dementia, multiple sclerosis, Huntington's disease, amyotrophic lateral sclerosis and Parkinson's disease. Since TSPO is also involved in the transport of cell proliferation precursor proteins to mitochondria, its effects in some malignancies are also being studied. In our study, we aimed to investigate the roles of TSPO in various physiopathological processes and to evaluate it as a potential diagnostic and therapeutic target.

Keywords

• Benzodiazepine
• TSPO
• Ro5-4864
• mitochondria
• inflammation
• apoptosis
• cancer

TSPO’nun (18 kDa Translokatör Protein) Yapısı, İşlevi ve Patolojik Süreçlerdeki Rolü

Abstract

Farmakolojik ve yapısal olarak santral benzodiazepin reseptörlerinden farklı olan TSPO, ilk olarak böbrekte diazepam için bağlanma alanı olarak keşfedilmiş ve beyin dışı yerleşimi nedeniyle “periferik benzodiazepin reseptörü” olarak tanımlanmıştır. Daha sonra periferik dokularla birlikte merkezi sinir sistemindeki glial hücreler, endotelyal hücreler ve bazı nöron popülasyonlarında da yüksek oranda bulunduğu tespit edildiğinden bu protein, “18 kDa Translokatör Protein (18 kDa TSPO)’’ olarak yeniden adlandırılmıştır. Mitokondri dış zarında yerleşik olan TSPO, hücre içindeki konumu itibariyle kolestrolün mitokondriye taşınmasını sağlayarak steroid sentezi, proliferasyon, inflamasyon ve apopitoz gibi birçok önemli süreçte rol oynamaktadır. TSPO’nun farklı patolojilerdeki etkilerinin araştırılması amacıyla Ro5-4864 ve PK11195 başta olmak üzere çeşitli TSPO ligandları kullanılmaktadır. TSPO ve ligandları; Alzheimer hastalığı (AH), frontotemporal demans, multipl skleroz, Huntington hastalığı, amyotrofik lateral skleroz ve Parkinson hastalığı gibi nörodejeneratif hastalıkların tanı ve tedavisinde önemli farmakolojik hedefler haline gelmiştir. Ayrıca hücre çoğalmasında öncül proteinlerin mitokondriye taşınmasında da görevli olduğundan bazı malignitelerdeki etkileri de incelenmektedir. Çalışmamızda TSPO’nun çeşitli fizyopatolojik süreçlerdeki rolleri ele alınarak potansiyel tanı ve tedavi hedefi olarak değerlendirilmesi amaçlanmıştır.

Keywords

• Benzodiazepin
• TSPO
• Ro5-4864
• mitokondri
• inflamasyon
• apopitoz
• kanser

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