Noori Alireza, Farhadi Kousha, Mohtasham Kia Yasmin, Hosseini Nastaran, Mehrabi Soraya
Division of Neuroscience, Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.
School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Mol Biol Rep. 2023 May;50(5):4535-4549. doi: 10.1007/s11033-023-08326-3. Epub 2023 Feb 28.
Parkinson's disease is a progressive neurodegenerative disorder caused by the degeneration of dopaminergic neurons. This leads to the pathogenesis of multiple basal ganglia-thalamomotor loops and diverse neurotransmission alterations. Dopamine replacement therapy, and on top of that, levodopa and l-3,4-dihydroxyphenylalanine (L-DOPA), is the gold standard treatment, while it develops numerous complications. Levodopa-induced dyskinesia (LID) is well-known as the most prominent side effect. Several studies have been devoted to tackling this problem. Studies showed that metabotropic glutamate receptor 5 (mGluR5) antagonists and 5-hydroxytryptamine receptor 1B (5HT1B) agonists significantly reduced LID when considering the glutamatergic overactivity and compensatory mechanisms of serotonergic neurons after L-DOPA therapy. Moreover, it is documented that these receptors act through an adaptor protein called P11 (S100A10). This protein has been thought to play a crucial role in LID due to its interactions with numerous ion channels and receptors. Lately, experiments have shown successful evidence of the effects of P11 blockade on alleviating LID greater than 5HT1B and mGluR5 manipulations. In contrast, there is a trace of ambiguity in the exact mechanism of action. P11 has shown the potential to be a promising target to diminish LID and prolong L-DOPA therapy in parkinsonian patients owing to further studies and experiments.
帕金森病是一种由多巴胺能神经元变性引起的进行性神经退行性疾病。这导致多个基底神经节 - 丘脑运动环路的发病机制和多种神经传递改变。多巴胺替代疗法，尤其是左旋多巴和L - 3,4 - 二羟基苯丙氨酸（L - DOPA），是金标准治疗方法，但其会引发众多并发症。左旋多巴诱导的异动症（LID）是最为突出的副作用。已有多项研究致力于解决这一问题。研究表明，在考虑L - DOPA治疗后谷氨酸能过度活跃和血清素能神经元的代偿机制时，代谢型谷氨酸受体5（mGluR5）拮抗剂和5 - 羟色胺受体1B（5HT1B）激动剂可显著降低LID。此外，据记载，这些受体通过一种名为P11（S100A10）的衔接蛋白发挥作用。由于该蛋白与众多离子通道和受体相互作用，人们认为它在LID中起关键作用。最近，实验已成功证明P11阻断对减轻LID的效果优于5HT1B和mGluR5的调控。相比之下，其确切作用机制仍存在一定模糊性。由于进一步的研究和实验，P11已显示出有望成为减少帕金森病患者LID并延长L - DOPA治疗的靶点。
