Peran Protein Klotho Dan Asam Lemak Omega-3 Dalam Patogenesis Dan Terapi Penyakit Alzheimer: Tinjauan Literatur

Apriyanto Apriyanto, Fasli Jalal, Diniwati Mukhta, Rizki Edmi Edison

Sari


Penyakit Alzheimer (AD) merupakan gangguan neurodegeneratif progresif yang ditandai oleh penurunan fungsi kognitif, memori, dan perubahan perilaku, serta belum tersedia terapi kuratif yang efektif. Kompleksitas patogenesis AD yang mencakup akumulasi beta-amiloid (Aβ), stres oksidatif, dan neuroinflamasi mendorong pencarian strategi terapeutik baru yang menargetkan berbagai jalur molekuler secara simultan. Penelitian ini bertujuan untuk mengevaluasi peran protein Klotho dan asam lemak omega-3 rantai panjang sebagai agen neuroprotektif potensial dalam pencegahan dan penanganan AD. Metode yang digunakan berupa tinjauan literatur naratif berdasarkan artikel ilmiah yang diperoleh melalui pencarian sistematis di berbagai basis data ilmiah internasional antara Januari 2019 hingga Maret 2025. Hasil kajian menunjukkan bahwa protein Klotho berperan penting dalam menekan neuroinflamasi melalui jalur NLRP3/caspase-1, menstimulasi autofagi, serta meningkatkan pembersihan Aβ melalui pengaruh terhadap transporter di sawar darah otak. Asam lemak omega-3 seperti DHA (docosahexaenoic acid) dan EPA (eicosapentaenoic acid) memberikan efek neuroprotektif melalui mekanisme peningkatan integritas sawar darah otak, pengurangan stres oksidatif, dan perbaikan fungsi glifatik otak. Beberapa uji klinis juga menunjukkan bahwa kombinasi intervensi metabolik mampu meningkatkan fungsi kognitif dan struktur otak pada pasien AD. Dari hasil ini bahwa pendekatan multi-targeted yang mencakup Klotho, omega-3, dan aktivator metabolik menunjukkan prospek signifikan sebagai strategi terapi neurodegeneratif yang lebih efektif dan holistik terhadap Alzheimer.


Kata Kunci


Alzheimer; Klotho; Omega-3

Teks Lengkap:

PDF

Referensi


Abbott, V., Housden, B.E. and Houldsworth, A. (2025) ‘Could immunotherapy and regulatory T cells be used therapeutically to slow the progression of Alzheimer’s disease?’, Brain Communications, 7(2), p. fcaf092. Available at: https://doi.org/10.1093/braincomms/fcaf092.

Alzheimer’s, disease (2021) ‘Alzheimer’s disease facts and figures’, The Journal Of The Alzheimer’s Association, 17(3), pp. 327–406. Available at: https://doi.org/10.1002/alz.12328.

Azka, A.S. et al. (2025) ‘EFEKTIFITAS TERAPI NEBULIZER PADA PASIEN DENGAN PENYAKIT PARU OBSTRUKTIF KRONIK (PPOK) : LITERATURE REVIEW’, 12(4).

Chen, E.Y. and Zhu, S. (2025) ‘Klotho in Alzheimer’s Disease: Therapeutic Potential and’, International Conference on Biological Engineering and Medical Science [Preprint]. Available at: https://doi.org/10.54254/2753-8818/78/2024.19897.

Clemente-Suárez, V.J. et al. (2025) ‘Neuro-Nutrition and Exercise Synergy: Exploring the Bioengineering of Cognitive Enhancement and Mental Health Optimization’, Bioengineering, 12(2), p. 208. Available at: https://doi.org/10.3390/bioengineering12020208.

Fung, T. et al. (2022) ‘Klotho an Autophagy Stimulator as a Potential Therapeutic Target for Alzheimer’s Disease: A Review’, Biomedicines, 10(3), p. 705. Available at: https://doi.org/10.3390/biomedicines10030705.

Hajare, A.D., Dagar, N. and Gaikwad, A.B. (2025) ‘Klotho antiaging protein: molecular mechanisms and therapeutic potential in diseases’, Molecular Biomedicine, 6(1), p. 19. Available at: https://doi.org/10.1186/s43556-025-00253-y.

Jha, N.K. et al. (2019) ‘Nuclear factor‐kappa β as a therapeutic target for Alzheimer’s disease’, Journal of Neurochemistry, 150(2), pp. 113–137. Available at: https://doi.org/10.1111/jnc.14687.

Kalamara, T. et al. (2025) ‘Cognitive efficacy of omega‑3 fatty acids in Alzheimer’s disease: A systematic review and meta‑analysis’, Biomedical Reports, 22(4), p. 62. Available at: https://doi.org/10.3892/br.2025.1940.

Kousparou, C. et al. (2023) ‘DHA/EPA (Omega-3) and LA/GLA (Omega-6) as Bioactive Molecules in Neurodegenerative Diseases’, International Journal of Molecular Sciences, 24(13), p. 10717. Available at: https://doi.org/10.3390/ijms241310717.

Lange, K.W. (2020) ‘Omega-3 fatty acids and mental health’, Global Health Journal, 4(1), pp. 18–30. Available at: https://doi.org/10.1016/j.glohj.2020.01.004.

Li, N. et al. (2024) ‘ANGPTL4-mediated microglial lipid droplet accumulation: Bridging Alzheimer’s disease and obesity’, Neurobiology of Disease, 203, p. 106741. Available at: https://doi.org/10.1016/j.nbd.2024.106741.

Li, Y. et al. (2022) ‘Neuroprotective Effect of Stearidonic Acid on Amyloid β-Induced Neurotoxicity in Rat Hippocampal Cells’, Antioxidants, 11(12), p. 2357. Available at: https://doi.org/10.3390/antiox11122357.

Mora, I. et al. (2022) ‘Structured Long-Chain Omega-3 Fatty Acids for Improvement of Cognitive Function during Aging’, International Journal of Molecular Sciences, 23(7), p. 3472. Available at: https://doi.org/10.3390/ijms23073472.

Sehar, U. et al. (2022) ‘Amyloid Beta in Aging and Alzheimer’s Disease’, International Journal of Molecular Sciences, 23(21), p. 12924. Available at: https://doi.org/10.3390/ijms232112924.

Van Dyck, C.H. et al. (2023) ‘Lecanemab in Early Alzheimer’s Disease’, New England Journal of Medicine, 388(1), pp. 9–21. Available at: https://doi.org/10.1056/NEJMoa2212948.

Wei, B.-Z. et al. (2023) ‘The Relationship of Omega-3 Fatty Acids with Dementia and Cognitive Decline: Evidence from Prospective Cohort Studies of Supplementation, Dietary Intake, and Blood Markers’, The

American Journal of Clinical Nutrition, 117(6), pp. 1096–1109.

Available at: https://doi.org/10.1016/j.ajcnut.2023.04.001.

Wen, J. et al. (2024) ‘Unraveling the impact of Omega-3 polyunsaturated fatty acids on blood-brain barrier (BBB) integrity and glymphatic function’, Brain, Behavior, and Immunity, 115, pp. 335–355. Available at: https://doi.org/10.1016/j.bbi.2023.10.018.

Wood, A.H.R., Chappell, H.F. and Zulyniak, M.A. (2022) ‘Dietary and supplemental long-chain omega-3 fatty acids as moderators of cognitive impairment and Alzheimer’s disease’, European Journal of Nutrition, 61(2), pp. 589–604. Available at:

https://doi.org/10.1007/s00394-021-02655-4.

Yulug, B. et al. (2023) ‘Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial’, Translational Neurodegeneration, 12(1), p. 4. Available at: https://doi.org/10.1186/s40035-023-00336-2.




DOI: https://doi.org/10.33024/jikk.v12i9.20495

Refbacks

  • Saat ini tidak ada refbacks.


##submission.copyrightStatement##

##submission.license.cc.by-nc4.footer##

Pendidikan Dokter Universitas Malahayati Lampung


Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.