Penemuan Senyawa Modulator Target Protein Tau Sebagai Pendekatan Terapeutik Penyakit Alzheimer: Studi Literatur
Discovery Of Tau Protein-Targeting Modulator Compounds As A Therapeutic Approach For Alzheimer’s Disease: A Literature Review
Abstract
Penyakit Alzheimer (AD) merupakan tantangan kesehatan global dengan opsi terapeutik yang sangat terbatas. Patologi protein Tau, yang bermanifestasi sebagai agregat neurotoksik intraseluler, menunjukkan korelasi yang kuat dengan tingkat penurunan kognitif pada pasien, menjadikannya target utama untuk intervensi farmakologis. Tinjauan literatur ini bertujuan untuk menganalisis secara sistematis penemuan dan pengembangan senyawa modulator protein Tau dalam rentang waktu publikasi 2020-2025, dengan mengkaji mekanisme aksi molekuler, status uji praklinis dan klinis, serta prospek di masa depan. Metode yang digunakan adalah studi literatur dari basis data ilmiah utama seperti PubMed dan ScienceDirect. Hasil analisis mengidentifikasi empat strategi utama yang sedang dikembangkan: (1) inhibisi proses agregasi Tau; (2) modulasi modifikasi pasca-translasi (PTM) untuk mencegah hiperfosforilasi; (3) stabilisasi mikrotubulus untuk mengkompensasi hilangnya fungsi fisiologis Tau; dan (4) peningkatan klirens Tau patologis melalui imunoterapi dan pendekatan lainnya. Hasil uji klinis hingga saat ini menunjukkan hasil yang bervariasi, di mana beberapa kegagalan memberikan pelajaran penting mengenai pemilihan target, waktu intervensi, dan desain uji. Meskipun tantangan signifikan tetap ada, terutama terkait penetrasi sawar darah otak, pipeline terapi berbasis Tau terus berkembang. Kemajuan pesat dalam teknologi biomarker (misalnya, PET-Tau dan p-Tau plasma) dan pergeseran strategis menuju terapi kombinasi menandakan era baru yang menjanjikan dalam pengembangan obat untuk AD
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