Peran α-synuclein sebagai target terapi parkinsonisme pasca cedera kepala
https://doi.org/10.22146/bns.v19i1.61895 Prasetyo Tri Kuncoro(1*), Indarwati Setyaningsih(2), Mochammad Was’an(3)
(1) Fakultas Kedokteran, Universitas Jenderal Soedirman, Purwokerto
(2) Departemen Neurologi, Fakultas Kedokteran-Kesehatan Masyarakat dan Keperawatan Universitas Gadjah Mada, Yogyakarta
(3) Departemen Neurologi, Fakultas Kedokteran-Kesehatan Masyarakat dan Keperawatan Universitas Gadjah Mada, Yogyakarta
(*) Corresponding Author
Abstract
Parkinsonism or secondary Parkinson's is one of the disabilities of motor disorders caused by head injury. Laboratory and animal experimental studies in head injuries showed decreased neurons in the substantia nigra, dopamine metabolic changes, and α-synuclein pathological changes. Rapid loss of nigrostraital dopaminergic neurons and widespread accumulation of α-synuclein are the pathological hallmark of Parkinson’s Disease. The current hypothesis is that head injuries, especially severe head injury when combined with Parkinson gene mutations, have a strong association with Parkinson's events.
The interaction between excessive expression of α-synuclein with inflammation of the neurons induced by head injury mediates the degeneration of neurons through the nigrostriatal dopaminergic pathway. In addition, activation of microglia cells in striatum showed the effect of synthetic α-synuclein with neuronal inflammation in nigrostriatal dopaminergic pathway. α-Synuclein plays an important role in the pathophysiology of Parkinsonism after head injury. Therefore, identification of therapy with target α-synuclein is essential for reducing morbidity and improving patient’s quality of life. There are 3 strategies to reduce the toxicity of α-synuclein: reduce aggregation, decrease synthesis, and increase α-synuclein clearance. Caspase-1 inhibition can prevent α-synuclein aggregation. In addition, it can also be achieved by immunotherapy approach. α -Synuclein clearance can be increased by upregulating the activity of ubiquitin / proteasome system.
ABSTRAK
Parkinsonisme atau Parkinson sekunder merupakan salah satu disabilitas gangguan motorik yang disebabkan karena cedera kepala. Berdasarkan penelitian laboratorium dan hewan coba, pada cedera kepala terjadi penurunan jumlah neuron di substansia nigra, perubahan metabolisme dopamine, dan perubahan patologi α-synuclein. Pada penyakit Parkinson akan terjadi kehilangan yang cepat pada neuron dopaminergik nigrostriatal dan akumulasi luas dari a-synuclein. Hipotesis yang saat ini muncul adalah cedera kepala terutama cedera kepala berat ketika dikombinasikan dengan mutasi gen Parkinson, memiliki hubungan yang kuat dengan kejadian Parkinson.
Interaksi antara ekspresi berlebihan dari α-synuclein dengan inflamasi neuron yang diinduksi oleh cedera kepala memediasi degenerasi neuron melalui jalur dopaminergik nigrostriatal. Selain itu, juga terjadi aktivasi sel mikroglia pada striatum yang menunjukkan efek sinergi α-synuclein dengan inflamasi neuron pada jalur dopaminergik nigrostriatal. α-Synuclein memainkan peran penting pada patofisiologi Parkinsonism pascacedera kepala. Oleh karena itu, identifikasi terapi dengan target α-synuclein sangat penting untuk mengurangi morbiditas dan meningkatkan kualitas hidup pasien. Terdapat 3 strategi untuk melawan toksisitas yang dihasilkan oleh α-synuclein yaitu dengan menurunkan agregasi, menurunkan sintesis, dan meningkatkan clearance α-synuclein. Inhibisi caspase-1 dapat mencegah agregasi α-synuclein. Selain itu dapat pula dilakukan dengan pendekatan imunoterapi. Peningkatan bersihan α-synuclein dapat dilakukan dengan meningkatkan aktivitas ubiquitin/proteasome system.
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DOI: https://doi.org/10.22146/bns.v19i1.61895
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