POTENSI KOMBINASI AMIDO-BRIDGED NUCLEIC ACID MODIFIED ANTISENSE OLIGONUCLEOTIDES DENGAN POLYAMIDOAMINE DENDRIMER GENERASI 4 TERTARGET Α-SYNUCLEIN SEBAGAI TERAPI PARKINSON

Putu Aprilyanti Aristadewi, Adrian Wiryanata Gorintha, Andrea Ivena

Abstract


Parkinson adalah penyakit neurodegeneratif yang meningkat lebih cepat daripada gangguan neurologis lainnya. Saat ini pengobatan Parkinson menggunakan dopamine agonist dan levodopa, namun pengobatan ini memiliki efek samping seperti menurunkan nafsu makan dan tidak berfokus pada pencegahan kematian neuron. Salah satu protein yang berperan dalam patogenesis dari Parkinson adalah protein α-synuclein, di mana agregasi dan misfolding dari protein ini bersifat toksik pada neuron sehingga mendukung progresi Parkinson. Antisense oligonucleotide (ASO) yang dikombinasikan dengan amido-bridge nucleic acid (AmNA) diketahui memiliki efek untuk menekan ekspresi mRNA α-synuclein namun hanya sebagian kecil dosis yang terdistribusi ke jaringan target sehingga diperlukan karier yang stabil. Polyamidoamine (PAMAM) Dendrimer menjadi pilihan dengan kemampuan menembus Blood Brain Barrier dan menarget organ secara spesifik. Secara khusus, PAMAM Dendrimer Generasi 4 (PAMAM G4) dapat menghambat agregasi protein α-synuclein. Oleh karena itu, mengombinasikan potensi yang dimiliki oleh AmNA-ASO dengan PAMAM Dendrimer Generasi 4 menggunakan larutan HEPES buffer diharapkan mampu menjadi terapi Parkinson yang menjanjikan.


Keywords


AmNA-ASO, PAMAM Dendrimer, Parkinson

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DOI: https://doi.org/10.26618/aimj.v4i1.4985

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