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From the tyrosine hydroxylase hypothesis of Parkinson's disease to modern strategies: a short historical overview

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机构: [1]Institute of Medical Biochemistry, University of Veterinary Medicine Vienna, Vienna, Austria [2]Department of Traditional Chinese Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China [3]Department of Pathology, Faculty of Veterinary Medicine, Assiut University, Assiut, Egypt
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关键词: Parkinson's disease Tyrosine hydroxylase Neurodegeneration Neuroprotection

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A time span of 60 years covers the detection of catecholamines in the brain, their function in movement and correlation to Parkinson's disease (PD). The clinical findings that orally given l-DOPA can alleviate or even prevent akinesia gave great hope for the treatment of PD. Attention focused on the role of tyrosine hydroxylase (TH) as the rate-limiting enzyme in the formation of catecholamines. It became evident that the enzyme driven formation is lowered in PD. Such results could only be obtained from studying human brain samples demonstrating the necessity for human brain banks. Originally, a TH enzyme deficiency was suspected in PD. Studies were conducted on the enzyme properties: its induction and turnover, the complex regulation starting with cofactor requirements as tetrahydrobiopterin and ferrous iron, and the necessity for phosphorylation for activity as well as inhibition by toxins or regulatory feedback inhibition by catecholamines. In the course of time, it became evident that neurodegeneration and cell death of dopaminergic neurons is the actual pathological process and the decrease of TH a cophenomenon. Nevertheless, TH immunochemistry has ever since been a valuable tool to study neuronal pathways, neurodegeneration in various animal models of neurotoxicity and cell cultures, which have been used as well to test potential neuroprotective strategies.

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出版当年[2021]版:
大类 | 4 区 医学
小类 | 4 区 临床神经病学 4 区 神经科学
最新[2025]版:
大类 | 3 区 医学
小类 | 3 区 临床神经病学 3 区 神经科学
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出版当年[2020]版:
Q2 CLINICAL NEUROLOGY Q3 NEUROSCIENCES
最新[2023]版:
Q2 CLINICAL NEUROLOGY Q2 NEUROSCIENCES

影响因子: 最新[2023版] 最新五年平均 出版当年[2020版] 出版当年五年平均 出版前一年[2019版] 出版后一年[2021版]

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第一作者机构: [1]Institute of Medical Biochemistry, University of Veterinary Medicine Vienna, Vienna, Austria
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