Plant-Derived Extracellular Vesicles in Brain Aging: Biological Properties and Molecular Mechanisms

Abstract

Beyin yaşlanması, sinir sistemi hastalıklarının büyük bir bölümünde görülen nörodejeneratif ve bilişsel bozuklukların temelini oluşturmakta, dünya genelinde önemli zorluklara yol açmakta ve küresel sağlık sistemleri üzerinde ciddi bir yük oluşturmaktadır. Beyin yaşlanmasında rol oynayan temel faktörler; ilerleyici nöronal işlev bozukluğu, kan beyin bariyerinin (KBB) bozulması, sinaptik kayıp, oksidatif stres ve kronik inflamasyon ile ilişkilendirilmiştir. Mevcut koruyucu ve tedavi edici yaklaşımlar, KBB’yi aşmadaki yetersizlik nedeniyle sınırlı etkinlik göstermekte olup, çoğunlukla kısa süreli ve sınırlı başarıya sahip farmakolojik ajanlara dayanmaktadır.  Doğal bitki temelli tedaviler, yara iyileşmesi, diyabet, obezite, inflamasyonla ilişkili hastalıklar ve kanser dahil olmak üzere birçok hastalığın tedavisinde yüksek etki potansiyeline sahip terapötik yaklaşımlar olarak yüzyıllardır kullanılmaktadır. Son on yılda, ileri nanoteknolojik gelişmeler sayesinde bitki kaynaklı terapötikler önemli bir aşama kaydetmiş; farmakolojik olmayan, güvenli ve maliyet etkin tedavi seçenekleri sunmuştur. Bitki kaynaklı ekstraselüler veziküller (PDEV’ler), kan beyin bariyerini aşabilen ve çeşitli hastalıklarda terapötik etki gösterebilen potansiyel doğal nanotaşıyıcılar olarak öne çıkmaktadır. PDEV’ler; mikroRNA’lar, lipidler ve proteinler gibi zengin biyoaktif moleküller içermeleri sayesinde antioksidan, anti-iflamatuar ve anti-apoptotik özellikler sergilemektedir. Güvenilirlikleri, biyouyumlulukları ve oral yolla uygulanabilir olmaları nedeniyle PDEV’ler, bilişsel gerilemeyi önlemeye ve sağlıklı beyin yaşlanmasını desteklemeye yönelik yeni ve non-invaziv bir yaklaşım sunmaktadır. Son dönemdeki preklinik çalışmalar, PDEV’lerin nöronal plastisiteyi ve nöron sağkalımını artırabileceğini, mikroglia ve astrosit aktivasyonunu module edebileceğini ve beyin yaşlanmasıyla ilişkili inflamasyon veya dolaşım bozukluklarını hafifletebileceğini göstermektedir. Bu derlemede, beyin yaşlanmasında PDEV’lerin terapötik potansiyeli; altta yatan temel mekanizmalar, kan beyin bariyerini geçiş özellikleri ve mevcut tedavilere kıyasla sundukları avantajlar çerçevesinde ele alınmıştır.

Keywords

• Beyin yaşlanması
• Ekstraselüler vezikül
• İnflamasyon
• Oksidatif stres

Beyin Yaşlanmasında Bitki Kaynaklı Ekstrasellüler Veziküller: Biyolojik Özellikler ve Moleküler Mekanizmalar

Abstract

Brain aging accounts for most of the neurodegenerative and cognitive impairments of all nervous system disorders, exhibiting significant challenges worldwide, and places a lot of burdens on global health care systems. The crucial factors for brain aging have been linked to progressive neuronal dysfunction, disruption of the blood brain barrier (BBB), synaptic loss, oxidative stress and chronic inflammation. The overall preventive and treatment methods involve reduced effectiveness due to poor access through the BBB and mostly depend on the use of pharmacological agents, which have limited success and short-term efficacy. Natural plant-based therapies have been used for centuries as therapeutics that offer higher impacts for the treatment of multiple disorders, including wound healing, diabetes, obesity, and inflammatory-related disorders, as well as cancer. Over the past decade, plant-derived therapeutics reached a milestone through advanced nanotechnology, providing non-pharmacological, safe, and cost-effective therapeutics. Plant-derived extracellular vesicles (PDEVs) have emerged as a potential natural nanocarriers capable of crossing the BBB and providing therapeutic effects in a variety of disorders. PDEVs demonstrate antioxidants, anti-inflammatory and anti-apoptotic properties with enriched bioactive molecules such as microRNAs, lipids, and proteins. Given their safety, biocompatibility, and oral administration, PDEVs provide a novel, non-invasive approach to combat cognitive decline and promote healthy brain aging. Recent preclinical studies claimed their potential to enhance neuronal plasticity, neuron survival, modulate microglial and astrocyte activation, alleviate inflammation or circulatory dysfunction associated with brain aging. In this review, we discussed the therapeutic potential of PDEVs in brain aging, focused on underlying crucial mechanisms, BBB-cross characteristics, and advantages over current therapies.

Keywords

• Brain aging
• Extracellular vesicle
• Inflammation
• oxidative stress

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